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Sample records for functionally related gene

  1. Detecting Mutual Functional Gene Clusters from Multiple Related Diseases

    E-print Network

    Buffalo, State University of New York

    Detecting Mutual Functional Gene Clusters from Multiple Related Diseases Nan Du, Xiaoyi Li, Yuan opportunity for understanding the functional genomics of a specific disease. Due to its strong power the gene clusters for various diseases. However, more and more evidence suggest that human diseases

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

    PubMed Central

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

    2015-01-01

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

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

    MedlinePLUS

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

  4. Relating Digital Information, Thermodynamic Stability, and Classes of Functional Genes in E. coli

    E-print Network

    Henkel, Werner

    Relating Digital Information, Thermodynamic Stability, and Classes of Functional Genes in E. coli Shannon and Gibbs entropy measures on the complete genome sequence of the bacteria Escherichia coli (E. coli). Furthermore, the link to the broader classes of functional gene groups (anabolic, catabolic

  5. Expression pattern and functions of autophagy-related gene atg5 in zebrafish organogenesis

    PubMed Central

    Hu, Zhanying; Zhang, Qingyou

    2011-01-01

    The implications of autophagy-related genes in serious neural degenerative diseases have been well documented. However, the functions and regulation of the family genes in embryonic development remain to be rigorously studied. Here, we report on for the first time the important role of atg5 gene in zebrafish neurogenesis and organogenesis as evidenced by the spatiotemporal expression pattern and functional analysis. Using morpholino oligo knockdown and mRNA overexpression, we demonstrated that zebrafish atg5 is required for normal morphogenesis of brain regionalization and body plan as well as for expression regulation of neural gene markers: gli1, huC, nkx2.2, pink1, ?-synuclein, xb51 and zic1. We further demonstrated that ATG5 protein is involved in autophagy by LC3-II/LC3I ratio and rapamycin-induction experiments, and that ATG5 is capable of regulating expression of itself gene in the manner of a feedback inhibition loop. In addition, we found that expression of another autophagy-related gene, atg12, is maintained at a higher constant level like a housekeeping gene. This indicates that the formation of the ATG12–ATG5 conjugate may be dependent on ATG5 protein generation and its splicing, rather than on ATG12 protein in zebrafish. Importantly, in the present study, we provide a mechanistic insight into the regulation and functional roles of atg5 in development of zebrafish nervous system. PMID:22082871

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

    E-print Network

    Yi, Gang Man

    2009-05-15

    common function and are not constrained by gene expression or other properties. I tested the algorithm by analyzing genomes of a representative set of species. I identified species specific variation in percentage of clustered genes as well...

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

    PubMed

    Benítez-Burraco, Antonio; Boeckx, Cedric

    2015-01-01

    The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language. PMID:26136701

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

    PubMed Central

    Benítez-Burraco, Antonio; Boeckx, Cedric

    2015-01-01

    The sequencing of the genomes from extinct hominins has revealed that changes in some brain-related genes have been selected after the split between anatomically-modern humans and Neanderthals/Denisovans. To date, no coherent view of these changes has been provided. Following a line of research we initiated in Boeckx and Benítez-Burraco (2014a), we hypothesize functional links among most of these genes and their products, based on the existing literature for each of the gene discussed. The genes we focus on are found mutated in different cognitive disorders affecting modern populations and their products are involved in skull and brain morphology, and neural connectivity. If our hypothesis turns out to be on the right track, it means that the changes affecting most of these proteins resulted in a more globular brain and ultimately brought about modern cognition, with its characteristic generativity and capacity to form and exploit cross-modular concepts, properties most clearly manifested in language. PMID:26136701

  9. Next generation sequencing search for uromodulin gene variants related with impaired renal function.

    PubMed

    Gómez, Juan; Díaz-Corte, Carmen; Tranche, Salvador; Alvarez, Francisco; Iglesias, Sara; Alonso, Belén; Coto, Eliecer

    2015-09-01

    Uromodulin gene (UMOD) mutations have been linked to rare forms of mendelian dominant medullary cystic kidney disease and familial hyperuricemia. In addition, common single nucleotide polymorphisms in the UMOD promoter have been associated with the risk for impaired renal function and chronic kidney disease. Our main purpose was to identify UMOD variants related with impaired renal function in an elderly population. The UMOD gene was next generation sequenced in a total of 100 healthy individuals with normal or reduced renal function [measured as the rate of estimated glomerular filtration (eGFR)]. The identified missense changes and the common promoter rs12917707 polymorphism were determined in individuals with reduced (n = 88) and normal (n = 442) eGFR values. Allele and genotype frequencies were compared between the groups. We only identified a rare UMOD misense change, p.V458L, and the rare leu allele was significantly more frequent in a cohort of individuals with reduced (eGFR < 60) compared to normal eGFR (P = 0.02). The common rs12917707 polymorphism previously linked to renal function and kidney disease was not associated with impaired filtration rate in our cohort. We found a significant effect of the rare p.V458L variant on the value of estimated glomerular filtration. This finding deserves further validation in larger cohorts. PMID:26040415

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

    ERIC Educational Resources Information Center

    Gericke, Niklas Markus; Hagberg, Mariana

    2007-01-01

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

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

    PubMed

    Boldogköi, Zsolt

    2012-01-01

    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

  12. Stress-related genes and heroin addiction: a role for a functional FKBP5 haplotype

    PubMed Central

    Levran, O.; Peles, E.; Randesi, M.; Li, Y.; Rotrosen, J.; Ott, J.; Adelson, M.; Kreek, M. J.

    2015-01-01

    Summary Background Stress is a critical risk factor affecting both the development of and the relapse to drug addictions. Drug addictions are caused by genetic, environmental and drug-induced factors. The objective of this hypothesis-driven association study was to determine if genetic variants in stress-related genes are associated with heroin addiction. Methods 112 selected genetic variants in 26 stress-related genes were genotyped in 852 case subjects and 238 controls of predominantly European ancestry. The case subjects are former heroin addicts with a history of at least one year of daily multiple uses of heroin, treated at a methadone maintenance treatment program (MMTP). The two most promising SNPs were subsequently tested in an African-American sample comprising of 314 cases and 208 control individuals. Results Nineteen single nucleotide polymorphisms (SNPs) in 9 genes (AVP, CRHR1, CRHR2, FKBP5, NR3C2, AVPR1A, GAL, GLRA1, and NPY1R) showed nominally significant association with heroin addiction. The associations of two FKBP5 SNPs that are part of one haplotype block, rs1360780 (intron 2) and rs3800373 (the 3' untranslated region), remained significant after correction for multiple testing (Pcorrected =0.03; OR = 2.35, Pcorrected = 0.0018; OR = 2.85, respectively). The two SNPs also showed nominally significant association (P <0.05) with heroin addiction in an independent African-American cohort. FKBP5 is a co-chaperone that regulates glucocorticoid sensitivity. These FKBP5 SNPs were previously associated with diverse affective disorders and showed functional differences in gene expression and stress response. This study also supports our and others’ previous reports of association of the GAL SNP rs694066 and the AVPR1A SNPs rs11174811, rs1587097 and rs10784339 with heroin and general drug addiction, respectively. Conclusions This study suggests that variations in the FKBP5 gene contribute to the development of opiate addiction by modulating the stress response. These findings may enhance the understanding of the interaction between stress and heroin addiction. PMID:24845178

  13. Temperature-Related Reaction Norms of Gene Expression: Regulatory Architecture and Functional Implications

    PubMed Central

    Chen, Jun; Nolte, Viola; Schlötterer, Christian

    2015-01-01

    The environment has profound effects on the expression of many traits and reaction norms describe the expression dynamics of a trait across a broad range of environmental conditions. Here, we analyze gene expression in Drosophila melanogaster across four different developmental temperatures (13–29 °C). Gene expression is highly plastic with 83.3% of the genes being differentially expressed. We distinguished three components of plasticity: 1) Dynamics of gene expression intensity (sum of change), 2) direction of change, and 3) curvature of the reaction norm (linear vs. quadratic). Studying their regulatory architecture we found that all three plasticity components were most strongly affected by the number of different transcription factors (TFs) binding to the target gene. More TFs were found in genes with less expression changes across temperatures. Although the effect of microRNAs was weaker, we consistently noted a trend in the opposite direction. The most plastic genes were regulated by fewer TFs and more microRNAs than less plastic genes. Different patterns of plasticity were also reflected by their functional characterization based on gene ontology. Our results suggest that reaction norms provide an important key to understand the functional requirements of natural populations exposed to variable environmental conditions. PMID:25976350

  14. Functional analysis of multiple genomic signatures demonstrates that classification algorithms choose phenotype-related genes

    PubMed Central

    Shi, W; Bessarabova, M; Dosymbekov, D; Dezso, Z; Nikolskaya, T; Dudoladova, M; Serebryiskaya, T; Bugrim, A; Guryanov, A; Brennan, R J; Shah, R; Dopazo, J; Chen, M; Deng, Y; Shi, T; Jurman, G; Furlanello, C; Thomas, R S; Corton, J C; Tong, W; Shi, L; Nikolsky, Y

    2010-01-01

    Gene expression signatures of toxicity and clinical response benefit both safety assessment and clinical practice; however, difficulties in connecting signature genes with the predicted end points have limited their application. The Microarray Quality Control Consortium II (MAQCII) project generated 262 signatures for ten clinical and three toxicological end points from six gene expression data sets, an unprecedented collection of diverse signatures that has permitted a wide-ranging analysis on the nature of such predictive models. A comprehensive analysis of the genes of these signatures and their nonredundant unions using ontology enrichment, biological network building and interactome connectivity analyses demonstrated the link between gene signatures and the biological basis of their predictive power. Different signatures for a given end point were more similar at the level of biological properties and transcriptional control than at the gene level. Signatures tended to be enriched in function and pathway in an end point and model-specific manner, and showed a topological bias for incoming interactions. Importantly, the level of biological similarity between different signatures for a given end point correlated positively with the accuracy of the signature predictions. These findings will aid the understanding, and application of predictive genomic signatures, and support their broader application in predictive medicine. PMID:20676069

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

    PubMed Central

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

    2014-01-01

    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

  16. From Gene Networks to Gene Function

    PubMed Central

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

    2003-01-01

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

  17. Genetic Analysis of Genes Related to Tight Junction Function in the Korean Population with Non-Syndromic Hearing Loss

    PubMed Central

    Sagong, Borum; Cho, Hyun-Ju; Bae, Jae Woong; Kim, Jeongho; Lee, Jinwook; Park, Hong-Joon; Choi, Jae Young; Lee, Kyu-Yup; Kim, Un-Kyung

    2014-01-01

    Tight junctions (TJs) are essential components of eukaryotic cells, and serve as paracellular barriers and zippers between adjacent tissues. TJs are critical for normal functioning of the organ of Corti, a part of the inner ear that causes loss of sensorineural hearing when damaged. To investigate the relation between genes involved in TJ function and hereditary loss of sensorineural hearing in the Korean population, we selected the TJP2 and CLDN14 genes as candidates for gene screening of 135 Korean individuals. The TJP2 gene, mutation of which causes autosomal dominant non-syndromic hearing loss (ADNSHL), lies at the DFNA51 locus on chromosome 9. The CLDN14 gene, mutation of which causes autosomal recessive non-syndromic hearing loss (ARNSHL), lies at the DFNB29 locus on chromosome 21. In the present study, we conducted genetic analyses of the TJP2 and CLDN14 genes in 87 unrelated patients with ADNSHL and 48 unrelated patients with either ARNSHL or potentially sporadic hearing loss. We identified two pathogenic variations, c.334G>A (p.A112T) and c.3562A>G (p.T1188A), and ten single nucleotide polymorphisms (SNPs) in the TJP2 gene. We found eight non-pathogenic variations in the CLDN14 gene. These findings indicate that, whereas mutation of the TJP2 gene might cause ADNSHL, CLDN14 is not a major causative gene for ARNSHL in the Korean population studied. Our findings may improve the understanding of the genetic cause of non-syndromic hearing loss in the Korean population. PMID:24752540

  18. A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene

    PubMed Central

    Papassotiropoulos, A; Stefanova, E; Vogler, C; Gschwind, L; Ackermann, S; Spalek, K; Rasch, B; Heck, A; Aerni, A; Hanser, E; Demougin, P; Huynh, K-D; Luechinger, R; Klarhöfer, M; Novakovic, I; Kostic, V; Boesiger, P; Scheffler, K; de Quervain, D J-F

    2013-01-01

    Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) was significantly (P=7 × 10?8) associated with verbal memory performance in a cognitively healthy cohort from Switzerland (n=1073) and was replicated in a second cohort from Serbia (n=524; P=0.003). Gene expression studies showed CTNNBL1 genotype-dependent differences in beta-catenin-like protein 1 mRNA levels in the human cortex. Functional magnetic resonance imaging in 322 subjects detected CTNNBL1 genotype-dependent differences in memory-related brain activations. Converging evidence from independent experiments and different methodological approaches suggests a role for CTNNBL1 in human memory. PMID:22105620

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

    PubMed Central

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

    2011-01-01

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

  20. Functional variants in the catalase and myeloperoxidase genes, ambient air pollution, and respiratory-related school absences: an example of epistasis in gene-environment interactions.

    PubMed

    Wenten, Madé; Gauderman, W James; Berhane, Kiros; Lin, Pi-Chu; Peters, John; Gilliland, Frank D

    2009-12-15

    The individual effect of functional single nucleotide polymorphisms within the catalase and myeloperoxidase genes (CAT and MPO) has been studied in relation to asthma; however, their interrelationship with ambient air pollution exposures has yet to be determined. The authors investigated the interrelationships between variants in CAT and MPO, ambient air pollutants, and acute respiratory illness. Health information, air pollution, and incident respiratory-related school absences were ascertained in January-June 1996 for 1,136 Hispanic and non-Hispanic white US elementary schoolchildren as part of the prospective Children's Health Study. Functional and tagging single nucleotide polymorphisms for the CAT and MPO loci were genotyped. The authors found epistasis between functional polymorphisms in the CAT/MPO loci, which differed by levels of oxidant-stress-producing air pollutants. Risk of respiratory-related school absences was elevated for children with the CAT (G/G) and MPO (G/A or A/A) genes (relative risk = 1.35, 95% confidence interval: 1.03, 1.77; P-interaction = 0.005). The epistatic effect of CAT and MPO variants was most evident in communities exhibiting high ambient ozone levels (P-interaction = 0.03). The association of respiratory-illness absences with functional variants in CAT and MPO that differ by air pollution levels illustrates the need to consider genetic epistasis in assessing gene-environment interactions. PMID:19897513

  1. Renal function in relation to three candidate genes in a Chinese population.

    PubMed

    Wang, Ji-Guang; Liu, Lifang; Zagato, Laura; Xie, Jinxiang; Fagard, Robert; Jin, Kugen; Wang, Jinxiang; Li, Yan; Bianchi, Giuseppe; Staessen, Jan A; Liu, Lisheng

    2004-10-01

    We recently found in a white population that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), alpha-adducin (Gly460Trp), and aldosterone synthase (-344C/T) jointly influence renal function. We therefore investigated in a Chinese population the associations between the serum concentrations of creatinine and uric acid and these three genetic polymorphisms. We genotyped 471 ethnic Han Chinese subjects from 125 nuclear families recruited in northern China via random population sampling (75%) and at specialized hypertension clinics (25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. The participants were 39.7 years old and included 235 women (49.9%). The blood pressure measured at the subjects' homes averaged 126/80 mmHg. Mean values were 71 micromol/l for serum creatinine, 111 ml min(-1) 1.73 m(-2) for calculated creatinine clearance, and 236 micromol/l for serum uric acid. With adjustment for covariables, GEE analyses of single genes demonstrated that serum uric acid, but not serum creatinine, was positively associated with the ACE D allele. Serum uric acid concentrations were 15.8 micromol/l (95% confidence interval 3.3-28.2) and 25.7 micromol/l (11.1-40.2) higher in DD homozygotes than in ID and II subjects, respectively. Further GEE analyses of the three genes combined showed that the association between serum uric acid and the ACE polymorphism was confined to carriers of the alpha-adducin Gly and/or aldosterone synthase C alleles. Sensitivity analyses in parents and offspring separately as well as QTDT analyses were confirmatory. Among 114 informative offspring carrying the alpha-adducin Gly allele serum uric acid was significantly and positively associated with the transmission of the ACE D allele (beta=20.7 micromol/l). In conclusion, the present study extends our previous findings on the combined effects of the three candidate genes and supports the concept that these genetic polymorphisms jointly influence renal function. PMID:15378162

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

    PubMed Central

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

    2012-01-01

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

  3. [Functional analysis of vernalization-related gene VER17 in flower development using antisense RNA strategy in winter wheat].

    PubMed

    Xu, Wen-Zhong; Yong, Wei-Dong; Xu, Yun-Yuan; Liang, Tie-Bing; Bai, Wei; Chong, Kang; Tan, Ke-Hui; Xu, Zhi-Hong; Zhu, Zhi-Qing

    2005-02-01

    To understand the function of vernalization-related gene VER17 in winter wheat (Triticum aestivum L. cv. Jingdong No.1), an antisense RNA strategy was used. The antisense VER17 with a vector pBI121 was constructed and transformed into winter wheat by using the pollen-tube-pathway method. Fourteen independent transgenic plants transformed with antisense VER17 and five control transformants transformed with pBI121 blank vector were obtained and confirmed by GUS histochemical assay and PCR-Southern blot analysis. Phenotypes of T(0) and T(1) transgenic plants showed that the plants of the antisense VER17 transgenic lines degenerated top or basal spikelets and had delayed flowering time, which suggested that the VER17 gene functions in accelerating flowering and the development of the top or basal spikelets and the stamen which were impacted by vernalization treatment. PMID:15692181

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

    E-print Network

    Senf, Alexander J.

    2011-02-04

    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 ...

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

    PubMed Central

    2014-01-01

    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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Expression of Endometrial Immune-related Genes Possibly Functioning During Early Pregnancy in the Mare

    PubMed Central

    TACHIBANA, Yurika; NAKANO, Yasuko; NAGAOKA, Kentaro; KIKUCHI, Masato; NAMBO, Yasuo; HANEDA, Shingo; MATSUI, Motozumi; MIYAKE, Yo-ichi; IMAKAWA, Kazuhiko

    2012-01-01

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

  9. Expression and function of osteogenic genes runt-related transcription factor 2 and osterix in orthodontic tooth movement in rats

    PubMed Central

    Han, Jinyou; He, Hong

    2015-01-01

    Objective: To investigate the expression and function of osteogenic genes osterix (OSX) and runt-related transcription factor 2 (RUNX2) in the rat periodontal tissues under orthodontic force for the remodeling of the periodontal tissues. Methods: 24 Wistar rats were randomly divided into 4 groups of orthodontic tooth movements for 1, 3, and 7 days (experimental groups) and control group (without orthodontic force). The expression of RUNX2 and OSX in the periodontal tissues was analyzed using real time PCR for mRNA and Western blot analysis for protein. The data were also analyzed for involvement of the two genes in signal pathways using bioinformatics tools. Results: The mRNA levels of RUNX2 and OSX increased in the periodontal tissues after subjected to the orthodontic force for 1 to 7 days, with the highest level occurring at day 7. The relative expression levels of RUNX2 and OSX mRNA were 1.85±0.12, 304±0.06 and 4.16±0.068, and 1.52±0.09, 1.83±0.03 and 2.56±0.06 at day 1, 3 and 7, respectively. The results of Western blot analysis were consistent with the mRNA results. Conclusion: In orthodontic tooth movement, the expression of RUNX2 and OSX was upregulated as a result of external stimulation, suggesting that the two genes is involved in periodontal tissue remodeling and plays an important role in periodontal tissue remodeling. PMID:26617945

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

    SciTech Connect

    Rangwala, Shamina M. . E-mail: shamina.rangwala@novartis.com; Li, Xiaoyan; Lindsley, Loren; Wang, Xiaomei; Shaughnessy, Stacey; Daniels, Thomas G.; Szustakowski, Joseph; Nirmala, N.R.; Wu, Zhidan; Stevenson, Susan C.

    2007-05-25

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

  11. Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposon in Eutherians.

    PubMed

    Irie, Masahito; Yoshikawa, Masanobu; Ono, Ryuichi; Iwafune, Hirotaka; Furuse, Tamio; Yamada, Ikuko; Wakana, Shigeharu; Yamashita, Yui; Abe, Takaya; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2015-09-01

    Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16) causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1. PMID:26402067

  12. Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposon in Eutherians

    PubMed Central

    Irie, Masahito; Yoshikawa, Masanobu; Ono, Ryuichi; Iwafune, Hirotaka; Furuse, Tamio; Yamada, Ikuko; Wakana, Shigeharu; Yamashita, Yui; Abe, Takaya; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2015-01-01

    Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16) causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1. PMID:26402067

  13. Isolation and functional analysis of the pathogenicity-related gene VdPR3 from Verticillium dahliae on cotton.

    PubMed

    Zhang, Ya-Lin; Li, Zhi-Fang; Feng, Zi-Li; Feng, Hong-Jie; Zhao, Li-Hong; Shi, Yong-Qiang; Hu, Xiao-Ping; Zhu, He-Qin

    2015-11-01

    The fungal plant pathogen Verticillium dahliae is the causal agent of vascular wilt, a disease that can seriously diminish cotton fiber yield. The pathogenicity mechanism and the identity of the genes that interact with cotton during the infection process still remain unclear. In this study, we investigated the low-pathogenic, non-microsclerotium-producing mutant vdpr3 obtained in a previous study from the screening of a T-DNA insertional library of the highly virulent isolate Vd080; the pathogenicity-related gene (VdPR3) in wild-type strain Vd080 was cloned. Knockout mutants (?VdPR3) showed lower mycelium growth and obvious reduction in sporulation ability without microsclerotium formation. An evaluation of carbon utilization in mutants and wild-type isolate Vd080 demonstrated that mutants-lacking VdPR3 exhibited decreased cellulase and amylase activities, which was restored in the complementary mutants (?VdPR3-C) to levels similar to those of Vd080. ?VdPR3 postponed infectious events in cotton and showed a significant reduction in pathogenicity. Reintroduction of a functional VdPR3 copy into ?VdPR3-C restored the ability to infect cotton plants. These results suggest that VdPR3 is a multifunctional gene involved in growth development, extracellular enzyme activity, and virulence of V. dahliae on cotton. PMID:25652159

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

    PubMed Central

    2010-01-01

    Background Sucrose phosphate synthase (SPS) is an important component of the plant sucrose biosynthesis pathway. In the monocotyledonous Poaceae, five SPS genes have been identified. Here we present a detailed analysis of the wheat SPSII family in wheat. A set of homoeologue-specific primers was developed in order to permit both the detection of sequence variation, and the dissection of the individual contribution of each homoeologue to the global expression of SPSII. Results The expression in bread wheat over the course of development of various sucrose biosynthesis genes monitored on an Affymetrix array showed that the SPS genes were regulated over time and space. SPSII homoeologue-specific assays were used to show that the three homoeologues contributed differentially to the global expression of SPSII. Genetic mapping placed the set of homoeoloci on the short arms of the homoeologous group 3 chromosomes. A resequencing of the A and B genome copies allowed the detection of four haplotypes at each locus. The 3B copy includes an unspliced intron. A comparison of the sequences of the wheat SPSII orthologues present in the diploid progenitors einkorn, goatgrass and Triticum speltoides, as well as in the more distantly related species barley, rice, sorghum and purple false brome demonstrated that intronic sequence was less well conserved than exonic. Comparative sequence and phylogenetic analysis of SPSII gene showed that false purple brome was more similar to Triticeae than to rice. Wheat - rice synteny was found to be perturbed at the SPS region. Conclusion The homoeologue-specific assays will be suitable to derive associations between SPS functionality and key phenotypic traits. The amplicon sequences derived from the homoeologue-specific primers are informative regarding the evolution of SPSII in a polyploid context. PMID:20591144

  15. 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...

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

    PubMed Central

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

    2014-01-01

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

  17. Discovery of genes related to formothion resistance in oriental fruit fly (Bactrocera dorsalis) by a constrained functional genomics analysis.

    PubMed

    Kuo, T C-Y; Hu, C-C; Chien, T-Y; Chen, M J M; Feng, H-T; Chen, L-F O; Chen, C-Y; Hsu, J-C

    2015-06-01

    Artificial selection can provide insights into how insecticide resistance mechanisms evolve in populations. The underlying basis of such phenomena can involve complex interactions of multiple genes, and the resolution of this complexity first necessitates confirmation that specific genes are involved in resistance mechanisms. Here, we used a novel approach invoking a constrained RNA sequencing analysis to refine the discovery of specific genes involved in insecticide resistance. Specifically, for gene discovery, an additional constraint was added to the traditional comparisons of susceptible vs. resistant flies by the incorporation of a line in which insecticide susceptibility was 'recovered' within a resistant line by the removal of insecticide stress. In our analysis, the criterion for the classification of any gene as related to insecticide resistance was based on evidence for differential expression in the resistant line as compared with both the susceptible and recovered lines. The incorporation of this additional constraint reduced the number of differentially expressed genes putatively involved in resistance to 464, compared with more than 1000 that had been identified previously using this same species. In addition, our analysis identified several key genes involved in metabolic detoxification processes that showed up-regulated expression. Furthermore, the involvement of acetylcholinesterase, a known target for modification in insecticide resistance, was associated with three key nonsynonymous amino acid substitutions within our data. In conclusion, the incorporation of an additional constraint using a 'recovered' line for gene discovery provides a higher degree of confidence in genes identified to be involved in insecticide resistance phenomena. PMID:25702834

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

    PubMed Central

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

    2015-01-01

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

  19. Molecular characterization and functional analysis of three pathogenesis-related cytochrome P450 genes from Bursaphelenchus xylophilus (Tylenchida: Aphelenchoidoidea).

    PubMed

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

    2015-01-01

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

  20. FunGene: the functional gene pipeline and repository

    PubMed Central

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

    2013-01-01

    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

  1. Predicting gene function from images of cells

    E-print Network

    Jones, Thouis Raymond, 1971-

    2007-01-01

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

  2. Antisense display--a method for functional gene screening: evaluation in a cell-free system and isolation of angiogenesis-related genes.

    PubMed

    Yonekura, H; Migita, H; Sakurai, S; Wang, H; Harada, S; Abedin, M J; Yamagishi, S; Yamamoto, H

    1999-07-01

    Presented here is an antisense-oriented method for functional gene screening, which we propose naming 'antisense display'. In principle, it consists of four steps: (i) preparation of phosphorothioate antisense repertoires that would correspond to the Kozak's consensus sequence, (ii) subgroup screening to identify active antisense molecules that could cause changes in the cellular phenotypes concerned and (iii) RT-PCR cloning of cDNA with the 5[prime] sense complement and 3[prime] anchor primers and sequence determination, followed by (iv) functional assays of candidate genes. Cell-free translation in rabbit reticulocyte lysate revealed that 10mer or longer antisense effectively halted protein synthesis. This required the presence of RNase H, and was achieved without prior heat-denaturation of the RNA templates. Then, subpools of the 10mer repertoire were administered to human microvascular endothelial cells in culture, and screened for anti-angiogenic activities. A single species having the sequence 5[prime]-GGCTCATGGT-3[prime] consistently inhibited the endothelial cell growth under hypoxia. Through RT-PCR with the corresponding sense primer, we came across three candidate cDNAs. Experiments employing longer unique antisense reproduced marked growth inhibitions in two of the three cDNAs. One encoded a mitochondrial protein and the other, which encoded a putative type-2 membrane protein containing Rab-GAP/TBC and EF-hand like domains, was a gene previously undescribed in human. The results suggest that the antisense display method is potentially useful for isolating new genes towards elucidating their functions. PMID:10373574

  3. The Origin, Expression, Function and Future Research Focus of a G Protein-coupled Receptor, Mas-related Gene X2 (MrgX2).

    PubMed

    Wu, Haihui; Zeng, Meiqi; Cho, Eric Y P; Jiang, Wenqi; Sha, Ou

    2015-07-01

    Mas-related genes (Mrgs) belong to a large family of G protein-coupled receptor genes found in rodents. Human MRGX proteins are G protein-coupled 7-transmembrane proteins sharing 41-52% amino acid identity with each other, but have no orthologs in rodents. MrgX2 is a member of the MrgX family. MRGX2 is expressed in the small neurons of sensory ganglia and mast cells. It can interact with a series of factors and genes such as the peptides substance P, vasoactive intestinal peptide, cortistatin (CST), proadrenomedullin N-terminal peptide (PAMP), LL-37, PMX-53 and ?-defensins. MRGX2 is related to nociception, adrenal gland secretion and mast cell degranulation. Recent research on MrgX2 provides insights into its role in nociception and anti-microbial activities. This article reviewed the origin, expression and function of MrgX2, and discussed possible future research focus. PMID:26106044

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

    PubMed Central

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

    1999-01-01

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

  5. Connectionist Approaches for Predicting Mouse Gene Function from Gene Expression

    E-print Network

    Bonner, Anthony

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

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

    E-print Network

    Kodysh, Yuliya

    2007-01-01

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

  7. A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions.

    PubMed

    Oikkonen, J; Huang, Y; Onkamo, P; Ukkola-Vuoti, L; Raijas, P; Karma, K; Vieland, V J; Järvelä, I

    2015-02-01

    Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested. We performed a genome-wide scan in 76 pedigrees (767 individuals) characterized for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception. Using the Bayesian linkage and association approach implemented in program package KELVIN, especially designed for complex pedigrees, several single nucleotide polymorphisms (SNPs) near genes affecting the functions of the auditory pathway and neurocognitive processes were identified. The strongest association was found at 3q21.3 (rs9854612) with combined SP, ST and KMT test scores (COMB). This region is located a few dozen kilobases upstream of the GATA binding protein 2 (GATA2) gene. GATA2 regulates the development of cochlear hair cells and the inferior colliculus (IC), which are important in tonotopic mapping. The highest probability of linkage was obtained for phenotype SP at 4p14, located next to the region harboring the protocadherin 7 gene, PCDH7. Two SNPs rs13146789 and rs13109270 of PCDH7 showed strong association. PCDH7 has been suggested to play a role in cochlear and amygdaloid complexes. Functional class analysis showed that inner ear and schizophrenia-related genes were enriched inside the linked regions. This study is the first to show the importance of auditory pathway genes in musical aptitude. PMID:24614497

  8. A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

    PubMed Central

    Oikkonen, J.; Huang, Y.; Onkamo, P.; Ukkola-Vuoti, L.; Raijas, P.; Karma, K.; Vieland, V. J.; Järvelä, I.

    2014-01-01

    Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested. We performed a genome-wide scan in 76 pedigrees (767 individuals) characterized for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception. Using the Bayesian linkage and association approach implemented in program package KELVIN, especially designed for complex pedigrees, several SNPs near genes affecting the functions of the auditory pathway and neurocognitive processes were identified. The strongest association was found at 3q21.3 (rs9854612) with combined SP, ST and KMT test scores (COMB). This region is located a few dozen kilobases upstream of the GATA binding protein 2 (GATA2) gene. GATA2 regulates the development of cochlear hair cells and the inferior colliculus (IC), which are important in tonotopic mapping. The highest probability of linkage was obtained for phenotype SP at 4p14, located next to the region harboring the protocadherin 7 gene, PCDH7. Two SNPs rs13146789 and rs13109270 of PCDH7 showed strong association. PCDH7 has been suggested to play a role in cochlear and amygdaloid complexes. Functional class analysis showed that inner ear and schizophrenia related genes were enriched inside the linked regions. This study is the first to show the importance of auditory pathway genes in musical aptitude. PMID:24614497

  9. 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

    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

    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

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

    E-print Network

    Obradovic, Zoran

    and conditions have been used to extract interesting patterns from gene expression datasets. One goal of gene, what genes are expressed in diseased cells that are not expressed in healthy cells. Related work hasMining Association Rules among Gene Functions in Clusters of Similar Gene Expression Maps Li An1

  11. Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells.

    PubMed

    Thomas, C; Ely, G; James, C D; Jenkins, R; Kastan, M; Jedlicka, A; Burger, P; Wharen, R

    2001-06-01

    Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal DNA particles similar to double-minute chromosomes. The cells contained two other gene mutations that are associated with high-grade astrocytic tumors: extra-chromosomal amplification of the cyclin-dependent kinase-4 (CDK4) gene and a homozygous mutation within the PTEN tumor suppressor gene. Immunoblots revealed very high levels of EGFR, moderately increased expression of CDK4, and no detectable PTEN protein. The overexpressed SKMG-3 EGFRs responded to exogenous ligand and resembled normal rather than mutant receptors. A heterozygous mutation of the p53 gene (p53R282W) correlated with failure of radiation to induce the expression of cyclin-dependent kinase inhibitor p21waf1 or an early G1 cell cycle arrest. Although each of these gene mutations occurs in GBMs, SKMG-3 cells had an unusual genotype in that a p53 gene mutation co-existed with amplified EGFR genes. Nonetheless, the SKMG-3 cell line can be exploited as a model to study how oncogenic EGFR signals in GBM cells interact with over-expressed CDK4 and loss of PTEN to confer the malignant phenotype. PMID:11515790

  12. Computing Gene Functional Similarity Using Combined Graphs

    E-print Network

    Al-Mubaid, Hisham

    way to explore the functional relationships between genes. We conducted the evaluation on a dataset gene functions and identifying gene disease associations are also based on GO. Gene ontologyComputing Gene Functional Similarity Using Combined Graphs Anurag Nagar Hisham Al-Mubaid Said

  13. Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

    SciTech Connect

    Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L. . E-mail: leonguo@ha.mc.ntu.edu.tw

    2007-05-15

    Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification.

  14. Functional Grouping of Genes Using Spectral Clustering and Gene Ontology

    E-print Network

    Zell, Andreas

    Functional Grouping of Genes Using Spectral Clustering and Gene Ontology Nora Speer, Holger amounts of biological data. During the analysis of such data the need for a functional grouping of genes arises. In this paper, we propose a new method based on spectral clustering for the partitioning of genes

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. 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...

  18. Spectral Clustering Gene Ontology Terms to Group Genes by Function

    E-print Network

    Zell, Andreas

    Spectral Clustering Gene Ontology Terms to Group Genes by Function Nora Speer, Christian Spieth throughput me- thods like DNA microarrays, biologists are capable of producing huge amounts of data. During the analysis of such data the need for a group- ing of the genes according to their biological function arises

  19. Rotavirus gene structure and function.

    PubMed Central

    Estes, M K; Cohen, J

    1989-01-01

    Knowledge of the structure and function of the genes and proteins of the rotaviruses has expanded rapidly. Information obtained in the last 5 years has revealed unexpected and unique molecular properties of rotavirus proteins of general interest to virologists, biochemists, and cell biologists. Rotaviruses share some features of replication with reoviruses, yet antigenic and molecular properties of the outer capsid proteins, VP4 (a protein whose cleavage is required for infectivity, possibly by mediating fusion with the cell membrane) and VP7 (a glycoprotein), show more similarities with those of other viruses such as the orthomyxoviruses, paramyxoviruses, and alphaviruses. Rotavirus morphogenesis is a unique process, during which immature subviral particles bud through the membrane of the endoplasmic reticulum (ER). During this process, transiently enveloped particles form, the outer capsid proteins are assembled onto particles, and mature particles accumulate in the lumen of the ER. Two ER-specific viral glycoproteins are involved in virus maturation, and these glycoproteins have been shown to be useful models for studying protein targeting and retention in the ER and for studying mechanisms of virus budding. New ideas and approaches to understanding how each gene functions to replicate and assemble the segmented viral genome have emerged from knowledge of the primary structure of rotavirus genes and their proteins and from knowledge of the properties of domains on individual proteins. Localization of type-specific and cross-reactive neutralizing epitopes on the outer capsid proteins is becoming increasingly useful in dissecting the protective immune response, including evaluation of vaccine trials, with the practical possibility of enhancing the production of new, more effective vaccines. Finally, future analyses with recently characterized immunologic and gene probes and new animal models can be expected to provide a basic understanding of what regulates the primary interactions of these viruses with the gastrointestinal tract and the subsequent responses of infected hosts. Images PMID:2556635

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

    PubMed Central

    Moon, Jisook

    2015-01-01

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

  1. Functional microarray analysis of differentially expressed genes in granulosa cells from women with polycystic ovary syndrome related to MAPK/ERK signaling

    PubMed Central

    Lan, Chen-Wei; Chen, Mei-Jou; Tai, Kang-Yu; Yu, Danny CW; Yang, Yu-Chieh; Jan, Pey-Shynan; Yang, Yu-Shih; Chen, Hsin-Fu; Ho, Hong-Nerng

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Although its aetiology and pathogenesis remain unclear, recent studies suggest that the dysfunction of granulosa cells may partly be responsible. This study aimed to use cDNA microarray technology to compare granulosa cell gene expression profiles in women with and without PCOS to identify genes that may be aetiologically implicated in the pathogenesis of PCOS. The study cohort included 12 women undergoing in vitro fertilization, six with PCOS and six without PCOS. Differential gene expression profiles were classified by post-analyses of microarray data, followed by western blot analyses to confirm the microarray data of selected genes. In total, 243 genes were differentially expressed (125 upregulated and 118 downregulated) between the PCOS and non-PCOS granulosa cells. These genes are involved in reproductive system development, amino acid metabolism and cellular development and proliferation. Comparative analysis revealed genes involved in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) signaling pathways. Western blot analyses confirmed that mitogen-activated protein kinase kinase kinase 4 and phospho-ERK1/2 were decreased in PCOS granulosa cells. This study identified candidate genes involved in MAPK/ERK signaling pathways that may influence the function of granulosa cells in PCOS. PMID:26459919

  2. 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)

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

    2014-01-01

    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.

  3. Yeast chromosome III: new gene functions.

    PubMed Central

    Koonin, E V; Bork, P; Sander, C

    1994-01-01

    One year after the release of the sequence of yeast chromosome III, we have re-examined its open reading frames (ORFs) by computer methods. More than 61% of the 171 probable gene products have significant sequence similarities in the current databases; as many as 54% have already known functions or are related to functionally characterized proteins, allowing partial prediction of protein function, 11 percentage points more than reported a year ago; 19% are similar to proteins of known three-dimensional structure, allowing model building by homology. The most interesting new identifications include a sugar kinase distantly related to ribokinases, a phosphatidyl serine synthetase, a putative transcription regulator, a flavodoxin-like protein, and a zinc finger protein belonging to a distinct subfamily. Several ORFs have similarities to uncharacterized proteins, resulting in new families in search of a function'. About 54% of ORFs match sequences from other phyla, including numerous fragments in the database of expressed sequence tags (ESTs). Most significant similarities to ESTs are with proteins in conserved families widely represented in the databases. About 30% of ORFs contain one or more predicted transmembrane segments. The increase in the power of functional and structural prediction comes from improvements in sequence analysis and from richer databases and is expected to facilitate substantially the experimental effort in characterizing the function of new gene products. Images PMID:8313894

  4. Gene polymorphisms associated with functional dyspepsia

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2010-01-01

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

  6. Gene function prediction using labeled and unlabeled data

    PubMed Central

    Zhao, Xing-Ming; Wang, Yong; Chen, Luonan; Aihara, Kazuyuki

    2008-01-01

    Background In general, gene function prediction can be formalized as a classification problem based on machine learning technique. Usually, both labeled positive and negative samples are needed to train the classifier. For the problem of gene function prediction, however, the available information is only about positive samples. In other words, we know which genes have the function of interested, while it is generally unclear which genes do not have the function, i.e. the negative samples. If all the genes outside of the target functional family are seen as negative samples, the imbalanced problem will arise because there are only a relatively small number of genes annotated in each family. Furthermore, the classifier may be degraded by the false negatives in the heuristically generated negative samples. Results In this paper, we present a new technique, namely Annotating Genes with Positive Samples (AGPS), for defining negative samples in gene function prediction. With the defined negative samples, it is straightforward to predict the functions of unknown genes. In addition, the AGPS algorithm is able to integrate various kinds of data sources to predict gene functions in a reliable and accurate manner. With the one-class and two-class Support Vector Machines as the core learning algorithm, the AGPS algorithm shows good performances for function prediction on yeast genes. Conclusion We proposed a new method for defining negative samples in gene function prediction. Experimental results on yeast genes show that AGPS yields good performances on both training and test sets. In addition, the overlapping between prediction results and GO annotations on unknown genes also demonstrates the effectiveness of the proposed method. PMID:18221567

  7. Functional characterization of the MKC1 gene of Candida albicans, which encodes a mitogen-activated protein kinase homolog related to cell integrity.

    PubMed Central

    Navarro-García, F; Sánchez, M; Pla, J; Nombela, C

    1995-01-01

    Mitogen-activated protein (MAP) kinases represent a group of serine/threonine protein kinases playing a central role in signal transduction processes in eukaryotic cells. Using a strategy based on the complementation of the thermosensitive autolytic phenotype of slt2 null mutants, we have isolated a Candida albicans homolog of Saccharomyces cerevisiae MAP kinase gene SLT2 (MPK1), which is involved in the recently outlined PKC1-controlled signalling pathway. The isolated gene, named MKC1 (MAP kinase from C. albicans), coded for a putative protein, Mkc1p, of 58,320 Da that displayed all the characteristic domains of MAP kinases and was 55% identical to S. cerevisiae Slt2p (Mpk1p). The MKC1 gene was deleted in a diploid Candida strain, and heterozygous and homozygous strains, in both Ura+ and Ura- backgrounds, were obtained to facilitate the analysis of the function of the gene. Deletion of the two alleles of the MKC1 gene gave rise to viable cells that grew at 28 and 37 degrees C but, nevertheless, displayed a variety of phenotypic traits under more stringent conditions. These included a low growth yield and a loss of viability in cultures grown at 42 degrees C, a high sensitivity to thermal shocks at 55 degrees C, an enhanced susceptibility to caffeine that was osmotically remediable, and the formation of a weak cell wall with a very low resistance to complex lytic enzyme preparations. The analysis of the functions downstream of the MKC1 gene should contribute to understanding of the connection of growth and morphogenesis in pathogenic fungi. PMID:7891715

  8. Discovery of Tumor Suppressor Gene Function.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.

    1995-01-01

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

  9. Functional Gene Networks: R/Bioc package to generate and analyse gene networks derived from functional enrichment and clustering

    PubMed Central

    Aibar, Sara; Fontanillo, Celia; Droste, Conrad; De Las Rivas, Javier

    2015-01-01

    Summary: Functional Gene Networks (FGNet) is an R/Bioconductor package that generates gene networks derived from the results of functional enrichment analysis (FEA) and annotation clustering. The sets of genes enriched with specific biological terms (obtained from a FEA platform) are transformed into a network by establishing links between genes based on common functional annotations and common clusters. The network provides a new view of FEA results revealing gene modules with similar functions and genes that are related to multiple functions. In addition to building the functional network, FGNet analyses the similarity between the groups of genes and provides a distance heatmap and a bipartite network of functionally overlapping genes. The application includes an interface to directly perform FEA queries using different external tools: DAVID, GeneTerm Linker, TopGO or GAGE; and a graphical interface to facilitate the use. Availability and implementation: FGNet is available in Bioconductor, including a tutorial. URL: http://bioconductor.org/packages/release/bioc/html/FGNet.html Contact: jrivas@usal.es Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25600944

  10. The dMRP/CG6214 gene of Drosophila is evolutionarily and functionally related to the human multidrug resistance-associated protein family.

    PubMed

    Tarnay, J N; Szeri, F; Iliás, A; Annilo, T; Sung, C; Le Saux, O; Váradi, A; Dean, M; Boyd, C D; Robinow, S

    2004-10-01

    ATP-binding cassette (ABC) transporters are involved in the transport of substrates across biological membranes and are essential for many cellular processes. Of the fifty-six Drosophila ABC transporter genes only white, brown, scarlet, E23 and Atet have been studied in detail. Phylogenetic analyses identify the Drosophila gene dMRP/CG6214 as an orthologue to the human multidrug-resistance associated proteins MRP1, MRP2, MRP3 and MRP6. To study evolutionarily conserved roles of MRPs we have initiated a characterization of dMRP. In situ hybridization and Northern analysis indicate that dMRP is expressed throughout development and appears to be head enriched in adults. Functional studies indicate that DMRP is capable of transporting a known MRP1 substrate and establishes DMRP as a high capacity ATP-dependent, vanadate-sensitive organic anion transporter. PMID:15373810

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

    PubMed Central

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

    2013-01-01

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

  12. Expression sensitivity analysis of human disease related genes.

    PubMed

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

    2013-01-01

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

  13. Antagonistic functional duality of cancer genes.

    PubMed

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

    2013-10-25

    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

  14. Functional Analysis of the Trichoderma harzianum nox1 Gene, Encoding an NADPH Oxidase, Relates Production of Reactive Oxygen Species to Specific Biocontrol Activity against Pythium ultimum?†

    PubMed Central

    Montero-Barrientos, M.; Hermosa, R.; Cardoza, R. E.; Gutiérrez, S.; Monte, E.

    2011-01-01

    The synthesis of reactive oxygen species (ROS) is one of the first events following pathogenic interactions in eukaryotic cells, and NADPH oxidases are involved in the formation of such ROS. The nox1 gene of Trichoderma harzianum was cloned, and its role in antagonism against phytopathogens was analyzed in nox1-overexpressed transformants. The increased levels of nox1 expression in these transformants were accompanied by an increase in ROS production during their direct confrontation with Pythium ultimum. The transformants displayed an increased hydrolytic pattern, as determined by comparing protease, cellulase, and chitinase activities with those for the wild type. In confrontation assays against P. ultimum the nox1-overexpressed transformants were more effective than the wild type, but not in assays against Botrytis cinerea or Rhizoctonia solani. A transcriptomic analysis using a Trichoderma high-density oligonucleotide (HDO) microarray also showed that, compared to gene expression for the interaction of wild-type T. harzianum and P. ultimum, genes related to protease, cellulase, and chitinase activities were differentially upregulated in the interaction of a nox1-overexpressed transformant with this pathogen. Our results show that nox1 is involved in T. harzianum ROS production and antagonism against P. ultimum. PMID:21421791

  15. Functional requirements driving the gene duplication in 12 Drosophila species

    PubMed Central

    2013-01-01

    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

  16. RNA Interference for Wheat Functional Gene Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2014-01-01

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

  18. Gene Function Prediction from Functional Association Networks Using Kernel Partial Least Squares Regression

    PubMed Central

    Lehtinen, Sonja; Lees, Jon; Bähler, Jürg; Shawe-Taylor, John; Orengo, Christine

    2015-01-01

    With the growing availability of large-scale biological datasets, automated methods of extracting functionally meaningful information from this data are becoming increasingly important. Data relating to functional association between genes or proteins, such as co-expression or functional association, is often represented in terms of gene or protein networks. Several methods of predicting gene function from these networks have been proposed. However, evaluating the relative performance of these algorithms may not be trivial: concerns have been raised over biases in different benchmarking methods and datasets, particularly relating to non-independence of functional association data and test data. In this paper we propose a new network-based gene function prediction algorithm using a commute-time kernel and partial least squares regression (Compass). We compare Compass to GeneMANIA, a leading network-based prediction algorithm, using a number of different benchmarks, and find that Compass outperforms GeneMANIA on these benchmarks. We also explicitly explore problems associated with the non-independence of functional association data and test data. We find that a benchmark based on the Gene Ontology database, which, directly or indirectly, incorporates information from other databases, may considerably overestimate the performance of algorithms exploiting functional association data for prediction. PMID:26288239

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

    PubMed Central

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

    2013-01-01

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

  20. The ubiquilin gene family: evolutionary patterns and functional insights

    PubMed Central

    2014-01-01

    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

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

    E-print Network

    Morris, Quaid

    , especially in gene therapy [18]. Identifying gene function in prokaryotes is much easier than eukaryotes dueNeural networks approaches for discovering the learnable correlation between gene function and gene Keywords: Gene function prediction Self organizing maps (SOM) Multilayer perceptrons (MLP) Gene expression

  2. Clock gene evolution and functional divergence.

    PubMed

    Tauber, Eran; Last, Kim S; Olive, Peter J W; Kyriacou, C P

    2004-10-01

    In considering the impact of the earth's changing geophysical conditions during the history of life, it is surprising to learn that the earth's rotational period may have been as short as 4 h, as recently as 1900 million years ago (or 1.9 billion years ago). The implications of such figures for the origin and evolution of clocks are considerable, and the authors speculate on how this short rotational period might have influenced the development of the "protoclock" in early microorganisms, such as the Cyanobacteria, during the geological periodsin which they arose and flourished. They then discuss the subsequent duplication of clock genes that took place around and after the Cambrian period, 543 million years ago, and its consequences. They compare the relative divergences of the canonical clock genes, which reveal the Per family to be the most rapidly evolving. In addition, the authors use a statistical test to predict which residues within the PER and CRY families may have undergone functional specialization. PMID:15534324

  3. Morpholinos: studying gene function in the chick

    PubMed Central

    Norris, Anneliese; Streit, Andrea

    2014-01-01

    The use of morpholinos for perturbing gene function in the chick, Gallus gallus, has led to many important discoveries in developmental biology. This technology makes use of in vivo electroporation, which allows gain and loss of function in a temporally, and spatially controlled manner. Using this method, morpholinos can be transfected into embryonic tissues from early to late developmental stages. In this article, we describe the methods currently used in our laboratory to knock down gene function using morpholinos in vivo. We also detail how morpholinos are used to provide consistency of the results, and describe two protocols to visualise the morpholino after electroporation. In addition, we provide guidance on avoiding potential pitfalls, and suggestions for troubleshooting solutions. These revised techniques provide a practical starting point for investigating gene function in the chick. PMID:24184187

  4. The fate of duplicated genes: loss or new function?

    E-print Network

    Wagner, Andreas

    mutations. Thus, as long as one duplicate gene functions normally, the other may go the more likely routeThe fate of duplicated genes: loss or new function? Andreas Wagner Summary Gene duplication events are important sources of novel gene functions. However, more often than not, a duplicate gene may lose its

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

    E-print Network

    Han, Bing

    2011-12-31

    an integrative method based on the bootstrapping K-S test to evaluate a large number of microarray datasets. The experimental results demonstrate that my method can find meaningful alterations in gene relations. For gene-gene interaction detection, I propose...

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

    E-print Network

    Kellis, Manolis

    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

  7. Studying Functions of All Yeast Genes Simultaneously

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Kalisky, Tomer; Dekel, Erez; Alon, Uri

    2007-12-01

    Cells respond to the environment by regulating the expression of genes according to environmental signals. The relation between the input signal level and the expression of the gene is called the gene regulation function. It is of interest to understand the shape of a gene regulation function in terms of the environment in which it has evolved and the basic constraints of biological systems. Here we address this by presenting a cost-benefit theory for gene regulation functions that takes into account temporally varying inputs in the environment and stochastic noise in the biological components. We apply this theory to the well-studied lac operon of E. coli. The present theory explains the shape of this regulation function in terms of temporal variation of the input signals, and of minimizing the deleterious effect of cell-cell variability in regulatory protein levels. We also apply the theory to understand the evolutionary tradeoffs in setting the number of regulatory proteins and for selection of feed-forward loops in genetic circuits. The present cost-benefit theory can be used to understand the shape of other gene regulatory functions in terms of environment and noise constraints.

  10. Review of Literature: Genes Related to Postaxial Polydactyly

    PubMed Central

    Verma, Prashant Kumar; El-Harouni, Ashraf A.

    2015-01-01

    Background: Postaxial polydactyly (PAP) is one of the commonest congenital malformations and usually is associated to several syndromes. There is no primary investigational strategy for PAP cases with single gene disorder in literature. PAP cases with single gene disorder can be classified according to common pathways and molecular basis. Molecular classification may help in diagnostic approach. Materials and Methods: All single gene disorders associated with PAP reported on PubMed and OMIM are analyzed and classified according to molecular basis. Results: Majority of genes related to cilia structure and functions are associated with PAP, so we classified them as ciliopathies and non-ciliopathies groups. Genes related to Shh–Gli3 pathway was the commonest group in non-ciliopathies. Conclusion: Genes related to cilia are most commonly related to PAP due to their indirect relationship to Shh–Gli3 signaling pathway. Initially, PAP may be the only clinical finding with ciliopathies so those cases need follow up. Proper diagnosis is helpful for management and genetic counseling. Molecular approach may help to define pleiotropy. PMID:25717468

  11. Functional characterization of FaNIP1;1 gene, a ripening-related and receptacle-specific aquaporin in strawberry fruit.

    PubMed

    Molina-Hidalgo, Francisco J; Medina-Puche, Laura; Gelis, Samuel; Ramos, José; Sabir, Farzana; Soveral, Graça; Prista, Catarina; Iglesias-Fernández, Raquel; Caballero, José L; Muñoz-Blanco, Juan; Blanco-Portales, Rosario

    2015-09-01

    Strawberry fruit (Fragaria × ananassa) is a soft fruit with high water content at ripe stage (more than 90% of its fresh weight). Aquaporins play an important role in plant water homeostasis, through the facilitation of water transport and solutes. We report the role played by FaNIP1;1 in the receptacle ripening process. The analysis by qRT-PCR of FaNIP1;1 showed that this gene is mainly expressed in fruit receptacle and has a ripening-related expression pattern that was accompanied by an increase in both the abscisic acid and water content of the receptacle throughout fruit ripening. Moreover, FaNIP1;1 was induced in situations of water deficit. Additionally, we show that FaNIP1;1 expression was positively regulated by abscisic acid and negatively regulated by auxins. The water transport capacity of FaNIP1;1 was determined by a stopped-flow spectroscopy in yeast over-expressing FaNIP1;1. Glycerol, H2O2 and boron transport were also demonstrated in yeast. On the other hand, GFP-FaNIP1;1 fusion protein was located in plasma membrane. In conclusion, FaNIP1;1 seems to play an important role increasing the plasma membrane permeability, that allows the water accumulation in the strawberry fruit receptacle throughout the ripening process. PMID:26259188

  12. Gene Transfers Between Distantly Related Organisms

    NASA Technical Reports Server (NTRS)

    Doolittle, Russell F.

    2003-01-01

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

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

    E-print Network

    Bonner, Anthony

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

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

    PubMed

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

    2009-01-01

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

  15. Sucrose metabolism gene families and their biological functions

    PubMed Central

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-01-01

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

  16. Sucrose metabolism gene families and their biological functions.

    PubMed

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-01-01

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

  17. Genome Function and Nuclear Architecture: From Gene Expression to Nanoscience

    E-print Network

    Langowski, Jörg

    Genome Function and Nuclear Architecture: From Gene Expression to Nanoscience Timothy P. O'Brien,1, and nanoscience approaches to the study of nuclear structure and activity have been developing recently and hold, and nanoscience to relate genome organization and nuclear archi- tecture with development and disease. Integrating

  18. Mutations in the pale aleurone color1 Regulatory Gene of the Zea mays Anthocyanin Pathway Have Distinct Phenotypes Relative to the Functionally Similar TRANSPARENT TESTA GLABRA1 Gene in Arabidopsis thalianaW?

    PubMed Central

    Carey, Charles C.; Strahle, Josie T.; Selinger, David A.; Chandler, Vicki L.

    2004-01-01

    The pale aleurone color1 (pac1) locus, required for anthocyanin pigment in the aleurone and scutellum of the Zea mays (maize) seed, was cloned using Mutator transposon tagging. pac1 encodes a WD40 repeat protein closely related to anthocyanin regulatory proteins ANTHOCYANIN11 (AN11) (Petunia hybrida [petunia]) and TRANSPARENT TESTA GLABRA1 (TTG1) (Arabidopsis thaliana). Introduction of a 35S-Pac1 transgene into A. thaliana complemented multiple ttg1 mutant phenotypes, including ones nonexistent in Z. mays. Hybridization of Z. mays genomic BAC clones with the pac1 sequence identified an additional related gene, mp1. PAC1 and MP1 deduced protein sequences were used as queries to build a phylogenetic tree of homologous WD40 repeat proteins, revealing an ancestral gene duplication leading to two clades in plants, the PAC1 clade and the MP1 clade. Subsequent duplications within each clade have led to additional WD40 repeat proteins in particular species, with all mutants defective in anthocyanin expression contained in the PAC1 clade. Substantial differences in pac1, an11, and ttg1 mutant phenotypes suggest the evolutionary divergence of regulatory mechanisms for several traits that cannot be ascribed solely to divergence of the dicot and monocot protein sequences. PMID:14742877

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

    SciTech Connect

    Chen, Z.Y.; Battinelli, E.M.; Hendriks, R.W.; Craig, I.W.; Powell, J.F.; Middleton-Price, H.; Sims, K.B.; Breakefield, X.O.

    1993-05-01

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

  20. Rice functionality, starch structure and the genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2014-05-01

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

  2. The systematic functional characterisation of Xq28 genes prioritises candidate disease genes

    PubMed Central

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

    2006-01-01

    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

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

    PubMed Central

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

    2015-01-01

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

  4. Visually Relating Gene Expression and in vivo DNA Binding Data

    SciTech Connect

    Huang, Min-Yu; Mackey, Lester; Ker?; nen, Soile V. E.; Weber, Gunther H.; Jordan, Michael I.; Knowles, David W.; Biggin, Mark D.; Hamann, Bernd

    2011-09-20

    Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative.

  5. Structure and Function of Fusion Gene Products in

    E-print Network

    Spang, Rainer

    Structure and Function of Fusion Gene Products in Childhood Acute Leukemia #12;Chromosomal;Transcriptional Activation RNA Polymerase II Gene Transcription Histon Acetylation Complex Chromatin Remodeling

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

    PubMed Central

    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

    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

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

    PubMed Central

    Guidarelli, Michela; Baraldi, Elena

    2015-01-01

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

  8. Characterization and expression analysis of a Retinoblastoma-related gene from Chinese wild Vitis pseudoreticulata

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Retinoblastoma-related (RBR) genes, a conserved gene family in higher eukaryotes, plays an important role in cell differentiation, development and mammalian cell death in animals; however, little is known about its function in plants. In this study, an RBR gene was isolated from the Chinese wild gr...

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. 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...

  13. Genome Analysis Maintenance of duplicate genes and their functional

    E-print Network

    Zhang, Jianzhi

    Genome Analysis Maintenance of duplicate genes and their functional redundancy by reduced- gence between duplicate genes, many old duplicates still maintain a high degree of functional similarity- tion of their ancestral functions. Consistent with this hypothesis, gene expression data from both

  14. Functional relations for various multiple zeta-functions

    E-print Network

    Tsumura, Hirofumi

    certain functional relations among Witten zeta-functions associated with semisimple Lie algebras (see [18#12;Functional relations for various multiple zeta-functions (Kohji Matsumoto) Graduate School Metropolitan University 1. INTRODUCTION The Euler-Zagier multiple zeta-function of depth $r$ is defined

  15. 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...

  16. Combining gene sequence similarity and textual information for gene function annotation in the literature

    E-print Network

    Kihara, Daisuke

    Ontology terms for target genes. Empirical studies on two testbeds demonstrate that the combination as an important information source for gene function annotation. The automatic process of function annotation from

  17. INVESTIGATION Gene Functional Trade-Offs and the Evolution

    E-print Network

    Otto, Sarah

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

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

    PubMed Central

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

    2015-01-01

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

  19. Physicochemical Evolution and Molecular Adaptation of the Cetacean Osmoregulation-related Gene UT-A2 and Implications for Functional Studies

    PubMed Central

    Wang, Jingzhen; Yu, Xueying; Hu, Bo; Zheng, Jinsong; Xiao, Wuhan; Hao, Yujiang; Liu, Wenhua; Wang, Ding

    2015-01-01

    Cetaceans have an enigmatic evolutionary history of re-invading aquatic habitats. One of their essential adaptabilities that has enabled this process is their homeostatic strategy adjustment. Here, we investigated the physicochemical evolution and molecular adaptation of the cetacean urea transporter UT-A2, which plays an important role in urine concentration and water homeostasis. First, we cloned UT-A2 from the freshwater Yangtze finless porpoise, after which bioinformatics analyses were conducted based on available datasets (including freshwater baiji and marine toothed and baleen whales) using MEGA, PAML, DataMonkey, TreeSAAP and Consurf. Our findings suggest that the UT-A2 protein shows folding similar to that of dvUT and UT-B, whereas some variations occurred in the functional So and Si regions of the selectivity filter. Additionally, several regions of the cetacean UT-A2 protein have experienced molecular adaptations. We suggest that positive-destabilizing selection could contribute to adaptations by influencing its biochemical and conformational character. The conservation of amino acid residues within the selectivity filter of the urea conduction pore is likely to be necessary for urea conduction, whereas the non-conserved amino acid replacements around the entrance and exit of the conduction pore could potentially affect the activity, which could be interesting target sites for future mutagenesis studies. PMID:25762239

  20. Physicochemical evolution and molecular adaptation of the cetacean osmoregulation-related gene UT-A2 and implications for functional studies.

    PubMed

    Wang, Jingzhen; Yu, Xueying; Hu, Bo; Zheng, Jinsong; Xiao, Wuhan; Hao, Yujiang; Liu, Wenhua; Wang, Ding

    2015-01-01

    Cetaceans have an enigmatic evolutionary history of re-invading aquatic habitats. One of their essential adaptabilities that has enabled this process is their homeostatic strategy adjustment. Here, we investigated the physicochemical evolution and molecular adaptation of the cetacean urea transporter UT-A2, which plays an important role in urine concentration and water homeostasis. First, we cloned UT-A2 from the freshwater Yangtze finless porpoise, after which bioinformatics analyses were conducted based on available datasets (including freshwater baiji and marine toothed and baleen whales) using MEGA, PAML, DataMonkey, TreeSAAP and Consurf. Our findings suggest that the UT-A2 protein shows folding similar to that of dvUT and UT-B, whereas some variations occurred in the functional So and Si regions of the selectivity filter. Additionally, several regions of the cetacean UT-A2 protein have experienced molecular adaptations. We suggest that positive-destabilizing selection could contribute to adaptations by influencing its biochemical and conformational character. The conservation of amino acid residues within the selectivity filter of the urea conduction pore is likely to be necessary for urea conduction, whereas the non-conserved amino acid replacements around the entrance and exit of the conduction pore could potentially affect the activity, which could be interesting target sites for future mutagenesis studies. PMID:25762239

  1. Functional analysis of the mospd gene family 

    E-print Network

    Buerger, Katrin

    2010-01-01

    Mospd3, a gene located on mouse chromosome 5, was identified in a gene trap screen in ES cells. The gene trap vector integration in multiple copies into the putative promoter of the gene, resulted in a loss of expression of Mospd3 at the trapped...

  2. PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees

    PubMed Central

    Mi, Huaiyu; Muruganujan, Anushya; Thomas, Paul D.

    2013-01-01

    The data and tools in PANTHER—a comprehensive, curated database of protein families, trees, subfamilies and functions available at http://pantherdb.org—have undergone continual, extensive improvement for over a decade. Here, we describe the current PANTHER process as a whole, as well as the website tools for analysis of user-uploaded data. The main goals of PANTHER remain essentially unchanged: the accurate inference (and practical application) of gene and protein function over large sequence databases, using phylogenetic trees to extrapolate from the relatively sparse experimental information from a few model organisms. Yet the focus of PANTHER has continually shifted toward more accurate and detailed representations of evolutionary events in gene family histories. The trees are now designed to represent gene family evolution, including inference of evolutionary events, such as speciation and gene duplication. Subfamilies are still curated and used to define HMMs, but gene ontology functional annotations can now be made at any node in the tree, and are designed to represent gain and loss of function by ancestral genes during evolution. Finally, PANTHER now includes stable database identifiers for inferred ancestral genes, which are used to associate inferred gene attributes with particular genes in the common ancestral genomes of extant species. PMID:23193289

  3. Mining the Gene Wiki for functional genomic knowledge

    PubMed Central

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Inference of Gene Relations from Microarray Data by Abduction

    E-print Network

    Sergot, Marek

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2006-01-01

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

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

    SciTech Connect

    Kawai, Shinji; Abiko, Yoshimitsu; Amano, Atsuo

    2010-07-23

    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.

  9. Evolution of new functions de novo and from preexisting genes.

    PubMed

    Andersson, Dan I; Jerlström-Hultqvist, Jon; Näsvall, Joakim

    2015-06-01

    How the enormous structural and functional diversity of new genes and proteins was generated (estimated to be 10(10)-10(12) different proteins in all organisms on earth [Choi I-G, Kim S-H. 2006. Evolution of protein structural classes and protein sequence families. Proc Natl Acad Sci 103: 14056-14061] is a central biological question that has a long and rich history. Extensive work during the last 80 years have shown that new genes that play important roles in lineage-specific phenotypes and adaptation can originate through a multitude of different mechanisms, including duplication, lateral gene transfer, gene fusion/fission, and de novo origination. In this review, we focus on two main processes as generators of new functions: evolution of new genes by duplication and divergence of pre-existing genes and de novo gene origination in which a whole protein-coding gene evolves from a noncoding sequence. PMID:26032716

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

    PubMed

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

    2010-08-01

    The arbuscular mycorrhiza association results from a successful interaction between genomes of the plant and fungal symbiotic partners. In this study, we analyzed the effect of inactivation of late-stage symbiosis-related pea genes on symbiosis-associated fungal and plant molecular responses in order to gain insight into their role in the functional mycorrhizal association. The expression of a subset of ten fungal and eight plant genes, previously reported to be activated during mycorrhiza development, was compared in Glomus intraradices-inoculated wild-type and isogenic genotypes of pea mutated for the PsSym36, PsSym33, and PsSym40 genes where arbuscule formation is inhibited or fungal turnover modulated, respectively. Microdissection was used to corroborate arbuscule-related fungal gene expression. Molecular responses varied between pea genotypes and with fungal development. Most of the fungal genes were downregulated when arbuscule formation was defective, and several were upregulated with more rapid fungal development. Some of the plant genes were also affected by inactivation of the PsSym36, PsSym33, and PsSym40 loci, but in a more time-dependent way during root colonization by G. intraradices. Results indicate a role of the late-stage symbiosis-related pea genes not only in mycorrhiza development but also in the symbiotic functioning of arbuscule-containing cells. PMID:20094894

  11. Network analysis of gene essentiality in functional genomics experiments.

    PubMed

    Jiang, Peng; Wang, Hongfang; Li, Wei; Zang, Chongzhi; Li, Bo; Wong, Yinling J; Meyer, Cliff; Liu, Jun S; Aster, Jon C; Liu, X Shirley

    2015-01-01

    Many genomic techniques have been developed to study gene essentiality genome-wide, such as CRISPR and shRNA screens. Our analyses of public CRISPR screens suggest protein interaction networks, when integrated with gene expression or histone marks, are highly predictive of gene essentiality. Meanwhile, the quality of CRISPR and shRNA screen results can be significantly enhanced through network neighbor information. We also found network neighbor information to be very informative on prioritizing ChIP-seq target genes and survival indicator genes from tumor profiling. Thus, our study provides a general method for gene essentiality analysis in functional genomic experiments ( http://nest.dfci.harvard.edu ). PMID:26518695

  12. Gene-environment interaction and male reproductive function

    PubMed Central

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

    2010-01-01

    As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring. PMID:20348940

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

    SciTech Connect

    Yavari, R.; Kinder, B.; Bale, A.E.

    1994-09-01

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

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

    PubMed

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

    2015-07-01

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

  15. Introduction GO FLNs GAIN Results Other Algorithms Gene Function Prediction

    E-print Network

    Zhang, Liqing

    Introduction GO FLNs GAIN Results Other Algorithms Gene Function Prediction T. M. Murali Department, 6, 11, 2011 T. M. Murali CS 3824 Gene Function Prediction #12;Introduction GO FLNs GAIN Results;Introduction GO FLNs GAIN Results Other Algorithms to the System Keith Haring, Untited, 1986 Urs Wehrli

  16. An overview of the goals and functions of the Israeli gene bank for agricultural crops

    E-print Network

    Novoplansky, Ariel

    An overview of the goals and functions of the Israeli gene bank for agricultural crops Rivka Hadas, The Israeli Gene Bank for Agricultural Crops, VolcaniCenter, Beit Dagan, Israel The area of Israel is rich in valuable wild-growing relatives of crop plants that can be used as breeding resources. However

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

    PubMed

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

    2013-01-01

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

  18. Identification of Immunity Related Genes to Study the Physalis peruviana – Fusarium oxysporum Pathosystem

    PubMed Central

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

    2013-01-01

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

  19. Chemical genomics for studying parasite gene function and interaction

    PubMed Central

    Li, Jian; Yuan, Jing; Chen, Chin-chien; Inglese, James; Su, Xin-zhuan

    2013-01-01

    With the development of new technologies in genome sequencing, gene expression profiling, genotyping, and high-throughput screening of chemical compound libraries, small molecules are playing increasingly important roles in studying gene expression regulation, gene-gene interaction, and gene function. Here we briefly review and discuss some recent advancements in drug target identification and phenotype characterization using combinations of high-throughput screening of small-molecule libraries and various genome-wide methods such as whole genome sequencing, genome-wide association studies, and genome-wide expressional analysis. These approaches can be used to search for new drugs against parasitic infections, to identify drug targets or drug-resistance genes, and to infer gene function. PMID:24215777

  20. Identifying genes related with rheumatoid arthritis via system biology analysis.

    PubMed

    Liu, Tao; Lin, Xinmei; Yu, Hongjian

    2015-10-15

    Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease that mainly attacks synovial joints. However, the underlying systematic relationship among different genes and biological processes involved in the pathogenesis are still unclear. By analyzing and comparing the transcriptional profiles from RA, OA (osteoarthritis) patients as well as ND (normal donors) with bioinformatics methods, we tend to uncover the potential molecular networks and critical genes which play important roles in RA and OA development. Initially, hierarchical clustering was performed to classify the overall transcriptional profiles. Differentially expressed genes (DEGs) between ND and RA and OA patients were identified. Furthermore, PPI networks were constructed, functional modules were extracted, and functional annotation was also applied. Our functional analysis identifies 22 biological processes and 2 KEGG pathways enriched in the commonly-regulated gene set. However, we found that number of set of genes differentially expressed genes only between RA and ND reaches up to 244, indicating this gene set may specifically accounts for processing to disease of RA. Additionally, 142 biological processes and 19 KEGG pathways are over-represented by these 244 genes. Meanwhile, although another 21 genes were differentially expressed only in OA and ND, no biological process nor pathway is over-represented by them. PMID:26117171

  1. Function does not follow form in gene regulatory circuits

    PubMed Central

    Payne, Joshua L.; Wagner, Andreas

    2015-01-01

    Gene regulatory circuits are to the cell what arithmetic logic units are to the chip: fundamental components of information processing that map an input onto an output. Gene regulatory circuits come in many different forms, distinct structural configurations that determine who regulates whom. Studies that have focused on the gene expression patterns (functions) of circuits with a given structure (form) have examined just a few structures or gene expression patterns. Here, we use a computational model to exhaustively characterize the gene expression patterns of nearly 17 million three-gene circuits in order to systematically explore the relationship between circuit form and function. Three main conclusions emerge. First, function does not follow form. A circuit of any one structure can have between twelve and nearly thirty thousand distinct gene expression patterns. Second, and conversely, form does not follow function. Most gene expression patterns can be realized by more than one circuit structure. And third, multifunctionality severely constrains circuit form. The number of circuit structures able to drive multiple gene expression patterns decreases rapidly with the number of these patterns. These results indicate that it is generally not possible to infer circuit function from circuit form, or vice versa. PMID:26290154

  2. Mining for Candidate Genes Related to Pancreatic Cancer Using Protein-Protein Interactions and a Shortest Path Approach

    PubMed Central

    Yuan, Fei; Zhang, Yu-Hang; Wan, Sibao; Wang, ShaoPeng; Kong, Xiang-Yin

    2015-01-01

    Pancreatic cancer (PC) is a highly malignant tumor derived from pancreas tissue and is one of the leading causes of death from cancer. Its molecular mechanism has been partially revealed by validating its oncogenes and tumor suppressor genes; however, the available data remain insufficient for medical workers to design effective treatments. Large-scale identification of PC-related genes can promote studies on PC. In this study, we propose a computational method for mining new candidate PC-related genes. A large network was constructed using protein-protein interaction information, and a shortest path approach was applied to mine new candidate genes based on validated PC-related genes. In addition, a permutation test was adopted to further select key candidate genes. Finally, for all discovered candidate genes, the likelihood that the genes are novel PC-related genes is discussed based on their currently known functions. PMID:26613085

  3. FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY

    PubMed Central

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

    2010-01-01

    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

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

    PubMed Central

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

    2005-01-01

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

  5. When natural selection gives gene function the cold shoulder.

    PubMed

    Cutter, Asher D; Jovelin, Richard

    2015-11-01

    It is tempting to invoke organismal selection as perpetually optimizing the function of any given gene. However, natural selection can drive genic functional change without improvement of biochemical activity, even to the extinction of gene activity. Detrimental mutations can creep in owing to linkage with other selectively favored loci. Selection can promote functional degradation, irrespective of genetic drift, when adaptation occurs by loss of gene function. Even stabilizing selection on a trait can lead to divergence of the underlying molecular constituents. Selfish genetic elements can also proliferate independent of any functional benefits to the host genome. Here we review the logic and evidence for these diverse processes acting in genome evolution. This collection of distinct evolutionary phenomena - while operating through easily understandable mechanisms - all contribute to the seemingly counterintuitive notion that maintenance or improvement of a gene's biochemical function sometimes do not determine its evolutionary fate. PMID:26411745

  6. Quantum affine algebras and universal functional relations

    E-print Network

    Kh. S. Nirov; A. V. Razumov

    2015-12-14

    By the universal integrability objects we mean certain monodromy-type and transfer-type operators, where the representation in the auxiliary space is properly fixed, while the representation in the quantum space is not. This notion is actually determined by the structure of the universal R-matrix. We call functional relations between such universal integrability objects, and so, being independent of the representation in the quantum space, the universal functional relations. We present a short review of the universal functional relations for the quantum integrable systems associated with the quantum groups of loop Lie algebras.

  7. Horizontal functional gene transfer from bacteria to fishes.

    PubMed

    Sun, Bao-Fa; Li, Tong; Xiao, Jin-Hua; Jia, Ling-Yi; Liu, Li; Zhang, Peng; Murphy, Robert W; He, Shun-Min; Huang, Da-Wei

    2015-01-01

    Invertebrates can acquire functional genes via horizontal gene transfer (HGT) from bacteria but fishes are not known to do so. We provide the first reliable evidence of one HGT event from marine bacteria to fishes. The HGT appears to have occurred after emergence of the teleosts. The transferred gene is expressed and regulated developmentally. Its successful integration and expression may change the genetic and metabolic repertoire of fishes. In addition, this gene contains conserved domains and similar tertiary structures in fishes and their putative donor bacteria. Thus, it may function similarly in both groups. Evolutionary analyses indicate that it evolved under purifying selection, further indicating its conserved function. We document the first likely case of HGT of functional gene from prokaryote to fishes. This discovery certifies that HGT can influence vertebrate evolution. PMID:26691285

  8. Horizontal functional gene transfer from bacteria to fishes

    PubMed Central

    Sun, Bao-Fa; Li, Tong; Xiao, Jin-Hua; Jia, Ling-Yi; Liu, Li; Zhang, Peng; Murphy, Robert W.; He, Shun-Min; Huang, Da-Wei

    2015-01-01

    Invertebrates can acquire functional genes via horizontal gene transfer (HGT) from bacteria but fishes are not known to do so. We provide the first reliable evidence of one HGT event from marine bacteria to fishes. The HGT appears to have occurred after emergence of the teleosts. The transferred gene is expressed and regulated developmentally. Its successful integration and expression may change the genetic and metabolic repertoire of fishes. In addition, this gene contains conserved domains and similar tertiary structures in fishes and their putative donor bacteria. Thus, it may function similarly in both groups. Evolutionary analyses indicate that it evolved under purifying selection, further indicating its conserved function. We document the first likely case of HGT of functional gene from prokaryote to fishes. This discovery certifies that HGT can influence vertebrate evolution. PMID:26691285

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

    PubMed

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

    2013-05-01

    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

  10. Virus Induced Gene Silencing for Functional Characterization of Genes Expressing in Various Wheat Tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Virus induced gene silencing (VIGS) has a great potential as a functional genomics tool. Methodological simplicity, robustness and speedy results make VIGS an ideal technique for high-throughput functional analysis of genes. In monocots, like wheat and barley, this technique has been shown to work...

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

    PubMed Central

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

    2006-01-01

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

  12. Genome-Wide Comparative Analysis of Flowering-Related Genes in Arabidopsis, Wheat, and Barley

    PubMed Central

    Peng, Fred Y.; Hu, Zhiqiu; Yang, Rong-Cai

    2015-01-01

    Early flowering is an important trait influencing grain yield and quality in wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) in short-season cropping regions. However, due to large and complex genomes of these species, direct identification of flowering genes and their molecular characterization remain challenging. Here, we used a bioinformatic approach to predict flowering-related genes in wheat and barley from 190 known Arabidopsis (Arabidopsis thaliana (L.) Heynh.) flowering genes. We identified 900 and 275 putative orthologs in wheat and barley, respectively. The annotated flowering-related genes were clustered into 144 orthologous groups with one-to-one, one-to-many, many-to-one, and many-to-many orthology relationships. Our approach was further validated by domain and phylogenetic analyses of flowering-related proteins and comparative analysis of publicly available microarray data sets for in silico expression profiling of flowering-related genes in 13 different developmental stages of wheat and barley. These further analyses showed that orthologous gene pairs in three critical flowering gene families (PEBP, MADS, and BBX) exhibited similar expression patterns among 13 developmental stages in wheat and barley, suggesting similar functions among the orthologous genes with sequence and expression similarities. The predicted candidate flowering genes can be confirmed and incorporated into molecular breeding for early flowering wheat and barley in short-season cropping regions. PMID:26435710

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

    PubMed

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

    2007-06-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

    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

  16. Calcitonin Gene-Related Peptide: Physiology and Pathophysiology

    PubMed Central

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

    2014-01-01

    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

  17. Introns within Ribosomal Protein Genes Regulate the Production and Function

    E-print Network

    Zhang, Jianzhi

    -specific phenotypic effects. Together, our results indicate that splicing in yeast RP genes mediates intergeneIntrons within Ribosomal Protein Genes Regulate the Production and Function of Yeast Ribosomes In budding yeast, the most abundantly spliced pre- mRNAs encode ribosomal proteins (RPs). To investi- gate

  18. Drosophila duplicate genes evolve new functions on the fly

    PubMed Central

    Assis, Raquel

    2014-01-01

    Gene duplication is thought to play a key role in phenotypic innovation. While several processes have been hypothesized to drive the retention and functional evolution of duplicate genes, their genomic contributions have never been determined. We recently developed the first genome-wide method to classify these processes by comparing distances between expression profiles of duplicate genes and their ancestral single-copy orthologs. Application of our approach to spatial gene expression profiles in two Drosophila species revealed that a majority of young duplicate genes possess new functions, and that new functions are acquired rapidly—often within a few million years. Surprisingly, new functions tend to arise in younger copies of duplicate gene pairs. Moreover, we found that young duplicates are often specifically expressed in testes, whereas old duplicates are broadly expressed across several tissues, providing strong support for the hypothetical “out-of-testes” origin of new genes. In this Extra View, I discuss our findings in the context of theoretical predictions about gene duplication, with a particular emphasis on the importance of natural selection in the evolution of novel phenotypes. PMID:25483247

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

    SciTech Connect

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

    2015-02-14

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

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

    DOE PAGESBeta

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

    2015-02-14

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

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

    PubMed Central

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

    2015-01-01

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

  2. Exploiting ontology graph for predicting sparsely annotated gene function

    PubMed Central

    Wang, Sheng; Cho, Hyunghoon; Zhai, ChengXiang; Berger, Bonnie; Peng, Jian

    2015-01-01

    Motivation: Systematically predicting gene (or protein) function based on molecular interaction networks has become an important tool in refining and enhancing the existing annotation catalogs, such as the Gene Ontology (GO) database. However, functional labels with only a few (<10) annotated genes, which constitute about half of the GO terms in yeast, mouse and human, pose a unique challenge in that any prediction algorithm that independently considers each label faces a paucity of information and thus is prone to capture non-generalizable patterns in the data, resulting in poor predictive performance. There exist a variety of algorithms for function prediction, but none properly address this ‘overfitting’ issue of sparsely annotated functions, or do so in a manner scalable to tens of thousands of functions in the human catalog. Results: We propose a novel function prediction algorithm, clusDCA, which transfers information between similar functional labels to alleviate the overfitting problem for sparsely annotated functions. Our method is scalable to datasets with a large number of annotations. In a cross-validation experiment in yeast, mouse and human, our method greatly outperformed previous state-of-the-art function prediction algorithms in predicting sparsely annotated functions, without sacrificing the performance on labels with sufficient information. Furthermore, we show that our method can accurately predict genes that will be assigned a functional label that has no known annotations, based only on the ontology graph structure and genes associated with other labels, which further suggests that our method effectively utilizes the similarity between gene functions. Availability and implementation: https://github.com/wangshenguiuc/clusDCA. Contact: jianpeng@illinois.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26072504

  3. Finding New Order in Biological Functions from the Network Structure of Gene Annotations.

    PubMed

    Glass, Kimberly; Girvan, Michelle

    2015-11-01

    The Gene Ontology (GO) provides biologists with a controlled terminology that describes how genes are associated with functions and how functional terms are related to one another. These term-term relationships encode how scientists conceive the organization of biological functions, and they take the form of a directed acyclic graph (DAG). Here, we propose that the network structure of gene-term annotations made using GO can be employed to establish an alternative approach for grouping functional terms that captures intrinsic functional relationships that are not evident in the hierarchical structure established in the GO DAG. Instead of relying on an externally defined organization for biological functions, our approach connects biological functions together if they are performed by the same genes, as indicated in a compendium of gene annotation data from numerous different sources. We show that grouping terms by this alternate scheme provides a new framework with which to describe and predict the functions of experimentally identified sets of genes. PMID:26588252

  4. Finding New Order in Biological Functions from the Network Structure of Gene Annotations

    PubMed Central

    Glass, Kimberly; Girvan, Michelle

    2015-01-01

    The Gene Ontology (GO) provides biologists with a controlled terminology that describes how genes are associated with functions and how functional terms are related to one another. These term-term relationships encode how scientists conceive the organization of biological functions, and they take the form of a directed acyclic graph (DAG). Here, we propose that the network structure of gene-term annotations made using GO can be employed to establish an alternative approach for grouping functional terms that captures intrinsic functional relationships that are not evident in the hierarchical structure established in the GO DAG. Instead of relying on an externally defined organization for biological functions, our approach connects biological functions together if they are performed by the same genes, as indicated in a compendium of gene annotation data from numerous different sources. We show that grouping terms by this alternate scheme provides a new framework with which to describe and predict the functions of experimentally identified sets of genes. PMID:26588252

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

    PubMed Central

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

    2012-01-01

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

  6. Functions of the gene products of Escherichia coli.

    PubMed Central

    Riley, M

    1993-01-01

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

  7. Ranking, selecting, and prioritising genes with desirability functions

    PubMed Central

    2015-01-01

    In functional genomics experiments, researchers often select genes to follow-up or validate from a long list of differentially expressed genes. Typically, sharp thresholds are used to bin genes into groups such as significant/non-significant or fold change above/below a cut-off value, and ad hoc criteria are also used such as favouring well-known genes. Binning, however, is inefficient and does not take the uncertainty of the measurements into account. Furthermore, p-values, fold-changes, and other outcomes are treated as equally important, and relevant genes may be overlooked with such an approach. Desirability functions are proposed as a way to integrate multiple selection criteria for ranking, selecting, and prioritising genes. These functions map any variable to a continuous 0–1 scale, where one is maximally desirable and zero is unacceptable. Multiple selection criteria are then combined to provide an overall desirability that is used to rank genes. In addition to p-values and fold-changes, further experimental results and information contained in databases can be easily included as criteria. The approach is demonstrated with a breast cancer microarray data set. The functions and an example data set can be found in the desiR package on CRAN (https://cran.r-project.org/web/packages/desiR/) and the development version is available on GitHub (https://github.com/stanlazic/desiR). PMID:26644980

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

    PubMed Central

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

    2008-01-01

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

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

    SciTech Connect

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

    2009-03-19

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

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

    SciTech Connect

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

    2011-10-07

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

  11. Regulation of Apoptosis-Related Genes by Nitric Oxide in Cancer

    PubMed Central

    Olson, Samuel Y.; Garbán, Hermes J.

    2008-01-01

    Nitric oxide (NO) is a simple molecule with a complex and pleitropic biological activity. NO or related species have been implicated in the regulation of many genes that participate in many diverse biological functions including programmed cell death or apoptosis. Apoptosis is a process that may potentially be disrupted in cancer cells conferring a survival advantage. In addition, malignant tumor cells can develop an intricate system of resistance to apoptotic stimuli. NO or related species have been shown to play a dual role in the regulation of apoptosis in malignant cells either promoting cell death or protecting cells from pro-apoptotic induction. However, the specific role of NO in the regulation of apoptosis/survival-related genes expression seems to tilt the balance toward the promotion of pro-apoptotic and the suppression of anti-apoptotic genes. Herein we have reviewed the most relevant aspects involving NO and/or reactive intermediates in the regulation of apoptosis-related genes –mainly– at the transcriptional level. We described the basic apoptotic molecules that potentially are affected by NO and how NO-mediated signaling gets transmitted to the transcriptional machinery that governs the expression of these genes. In addition, we discussed some of the fundamental functional consequences of the regulation of apoptosis-related genes by NO in cancer biology and its potential therapeutic implications. PMID:18460349

  12. Structure and function of the deleted in azoospermia gene 

    E-print Network

    Sprague, David Chase Cameron

    2009-05-15

    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...

  13. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    PubMed Central

    2011-01-01

    Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs. PMID:21729286

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

    E-print Network

    Sinskey, Anthony J.

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

  15. Genetic Regulation of Caenorhabditis elegans Lysosome Related Organelle Function

    PubMed Central

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

    2013-01-01

    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

  16. Identification of mycoparasitism-related genes in Clonostachys rosea 67-1 active against Sclerotinia sclerotiorum

    PubMed Central

    Sun, Zhan-Bin; Sun, Man-Hong; Li, Shi-Dong

    2015-01-01

    Clonostachys rosea is a mycoparasite that has shown great potential in controlling various plant fungal pathogens. In order to find mycoparasitism-related genes in C. rosea, the transcriptome of the efficient isolate 67-1 in association with sclerotia of Sclerotinia sclerotiorum was sequenced and analysed. The results identified 26,351 unigenes with a mean length of 1,102 nucleotides, among which 18,525 were annotated in one or more databases of NR, KEGG, Swiss-Prot, GO and COG. Differentially expressed genes at 8?h, 24?h and 48?h after sclerotial induction were analysed, and 6,890 unigenes were upregulated compared with the control without sclerotia. 713, 1,008 and 1,929 genes were specifically upregulated expressed, while 1,646, 283 and 529 genes were specifically downregulated, respectively. Gene ontology terms analysis indicated that these genes were mainly involved in metabolism of biological process, catalysis of molecular function and cellular component. The expression levels of 12 genes that were upregulated after encountering with S. sclerotiorum were monitored using real-time PCR. The results indicated that the quantitative detection was consistent with the transcriptome analysis. The study provides transcriptional gene expression information on C. rosea parasitizing S. sclerotiorum and forms the basis for further investigation of mycoparasitism-related genes of C. rosea. PMID:26657839

  17. Identification of mycoparasitism-related genes in Clonostachys rosea 67-1 active against Sclerotinia sclerotiorum.

    PubMed

    Sun, Zhan-Bin; Sun, Man-Hong; Li, Shi-Dong

    2015-01-01

    Clonostachys rosea is a mycoparasite that has shown great potential in controlling various plant fungal pathogens. In order to find mycoparasitism-related genes in C. rosea, the transcriptome of the efficient isolate 67-1 in association with sclerotia of Sclerotinia sclerotiorum was sequenced and analysed. The results identified 26,351 unigenes with a mean length of 1,102 nucleotides, among which 18,525 were annotated in one or more databases of NR, KEGG, Swiss-Prot, GO and COG. Differentially expressed genes at 8?h, 24?h and 48?h after sclerotial induction were analysed, and 6,890 unigenes were upregulated compared with the control without sclerotia. 713, 1,008 and 1,929 genes were specifically upregulated expressed, while 1,646, 283 and 529 genes were specifically downregulated, respectively. Gene ontology terms analysis indicated that these genes were mainly involved in metabolism of biological process, catalysis of molecular function and cellular component. The expression levels of 12 genes that were upregulated after encountering with S. sclerotiorum were monitored using real-time PCR. The results indicated that the quantitative detection was consistent with the transcriptome analysis. The study provides transcriptional gene expression information on C. rosea parasitizing S. sclerotiorum and forms the basis for further investigation of mycoparasitism-related genes of C. rosea. PMID:26657839

  18. The urease gene cluster of Vibrio parahaemolyticus does not influence the expression of the thermostable direct hemolysin (TDH) gene or the TDH-related hemolysin gene.

    PubMed

    Nakaguchi, Yoshitsugu; Okuda, Jun; Iida, Tetsuya; Nishibuchi, Mitsuaki

    2003-01-01

    In order to investigate why the thermostable direct hemolysin (TDH) and the TDH-related hemolysin (TRH) of Vibrio parahaemolyticus are produced at low levels from urease-positive strains, the effect of the functional urease gene cluster of V. parahaemolyticus on the expression of the tdh and trh genes was examined. Transcriptional lacZ fusions with the tdh1, tdh2, trh1 and trh2 genes representing variants of the tdh and trh genes were integrated into the chromosome of an Escherichia coli strain and a urease-negative V. parahaemolyticus strain. The plasmid-borne urease gene cluster introduced and expressed in these constructs did not affect expression of any of the fusion genes. The amount of TDH produced from a Kanagawa phenomenon-positive V. parahaemolyticus did not change by introduction of the urease gene cluster either. It was concluded therefore that the urease gene cluster is not involved in the regulation of tdh and trh expression. PMID:12725294

  19. Main Functions and Taxonomic Distribution of Virulence Genes in Brucella melitensis 16 M

    PubMed Central

    Brambila-Tapia, Aniel Jessica Leticia; Armenta-Medina, Dagoberto; Rivera-Gomez, Nancy; Perez-Rueda, Ernesto

    2014-01-01

    Many virulence genes have been detected in attenuated mutants of Brucella melitensis 16 M; nevertheless, a complete report of these genes, including the main Cluster of Orthologous Groups (COG) represented as well as the taxonomical distribution among all complete bacterial and archaeal genomes, has not been analyzed. In this work a total of 160 virulence genes that have been reported in attenuated mutants in B. melitensis were included and analyzed. Additionally, we obtained 250 B. melitensis randomly selected genes as a reference group for the taxonomical comparisons. The COGs and the taxonomical distribution profile for 789 nonredundant bacterial and archaeal genomes were obtained and compared with the whole-genome COG distribution and with the 250 randomly selected genes, respectively. The main COGs associated with virulence genes corresponded to the following: intracellular trafficking, secretion and vesicular transport (U); cell motility (N); nucleotide transport and metabolism (F); transcription (K); and cell wall/membrane/envelope biogenesis (M). In addition, we found that virulence genes presented a higher proportion of orthologs in the Euryarchaeota and Proteobacteria phyla, with a significant decrease in Chlamydiae, Bacteroidetes, Tenericutes, Firmicutes and Thermotogae. In conclusion, we found that genes related to specific functions are more relevant to B. melitensis virulence, with the COG U the most significant. Additionally, the taxonomical distribution of virulence genes highlights the importance of these genes in the related Proteobacteria, being less relevant in distant groups of organisms with the exception of Euryarchaeota. PMID:24964015

  20. Transferred interbacterial antagonism genes augment eukaryotic innate immune function.

    PubMed

    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

    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

  1. Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment

    PubMed Central

    Aenlle, Kristina K.; Foster, Thomas C.

    2009-01-01

    This study used microarray analysis to examine age-related changes in gene expression 6 and 12 hr following a single estradiol injection in ovariectomized mice. Estradiol-responsive gene expression at the 6 hr time point was reduced in aged (18 mo) animals compared to young (4 mo) and middle-aged (MA, 12 mo) mice. Examination of gene clustering within biological and functional pathways indicated that young and MA mice exhibited increased expression of genes for cellular components of the synapse and decreased expression of genes related to oxidative phosphorylation and mitochondrial dysfunction. At the 12 hr time point, estradiol-responsive gene expression increased in aged animals and decreased in young and MA mice compared to the 6 hr time point. Gene clustering analysis indicated that aged mice exhibited increased expression of genes for signaling pathways that are rapidly influenced by estradiol. The age differences in gene expression for rapid signaling pathways may relate to disparity in basal pathway activity and estradiol mediated activation of rapid signaling cascades. PMID:19790252

  2. Functioning haemoglobin genes in non-nodulating plants.

    PubMed

    Bogusz, D; Appleby, C A; Landsmann, J; Dennis, E S; Trinick, M J; Peacock, W J

    1988-01-14

    Haemoglobin has previously been recorded in plants only in the nitrogen-fixing nodules formed by symbiotic association between Rhizobium or Frankia and legume or non-legume hosts. Structural similarities amongst these and animal haemoglobins at the protein and gene level suggested a common evolutionary origin. This suggests that haemoglobin genes, inherited from an ancestor common to plants and animals, might be present in all plants. We report here the isolation of a haemoglobin gene from Trema tomentosa, a non-nodulating relative of Parasponia (Ulmaceae). The gene has three introns located at positions identical to those in the haemoglobin genes of nodulating plant species, strengthening the case for a common origin of all plant haemoglobin genes. The data argue strongly against horizontal haemoglobin gene transfer from animals to plants. The Trema gene has a tissue-specific pattern of transcription and translation, producing monomeric haemoglobin in Trema roots. We have also found that the Parasponia haemoglobin gene is transcribed in roots of non-nodulated plants. These results suggest that haemoglobin has a role in the respiratory metabolism of root cells of all plant species. We propose that its special role in nitrogen-fixing nodules has required adaptation of the haemoglobin-gene regulation pathway, to give high expression in the specialized environment of the nodule. PMID:2448639

  3. The role of inflammation-related genes in osteoarthritis.

    PubMed

    Rogers, E L; Reynard, L N; Loughlin, J

    2015-11-01

    In this review article we examine the role of inflammation-related genes in osteoarthritis (OA) from the perspective of genetics, epigenetics and gene expression. There have been great strides in such genomic analyses of OA in recent years thanks to the study of adequately powered patient cohorts, the detailed analysis of candidate genes, and the application of genome-wide approaches. These have led to some unexpected and therefore exciting discoveries, implicating pathways that would not necessarily have been predicted to have a role in this common arthritis. Inflammatory-related genes sit firmly in the candidate camp based on prior observations that the OA disease process can have an inflammatory component. What is clear from the genetic studies published to date is that there is no compelling evidence that DNA variation in inflammatory genes is an OA risk factor. This conclusion may of course change as ever more powerful association studies are conducted. There is, however, compelling evidence that epigenetic effects involving inflammatory genes are a component of OA and that alteration in the expression of these genes is also highly relevant to the disease process. We may in fact be close to demonstrating, at the genomic level, a clear separation of OA patients into those in whom inflammation is a key driver of the disease and those in whom it is not. This has obvious implications for the design of trials of novel OA interventions and may also guide the intelligent re-purposing of anti-inflammatory therapies. PMID:26521739

  4. A complex network analysis of hypertension-related genes

    NASA Astrophysics Data System (ADS)

    Wang, Huan; Xu, Chuan-Yun; Hu, Jing-Bo; Cao, Ke-Fei

    2014-01-01

    In this paper, a network of hypertension-related genes is constructed by analyzing the correlations of gene expression data among the Dahl salt-sensitive rat and two consomic rat strains. The numerical calculations show that this sparse and assortative network has small-world and scale-free properties. Further, 16 key hub genes (Col4a1, Lcn2, Cdk4, etc.) are determined by introducing an integrated centrality and have been confirmed by biological/medical research to play important roles in hypertension.

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

    PubMed Central

    2014-01-01

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

  6. Relations between Prosodic Variables and Communicative Functions.

    ERIC Educational Resources Information Center

    Flax, Judy; And Others

    1991-01-01

    Three children were observed interacting with their mothers before the onset of single words, when vocabulary consisted of 10 words, and when it consisted of 50 words. Relations between communicative functions and acoustic analysis of prosodic variables were studied. Considerable variability was found in the number of rises produced overall and…

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

    PubMed

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

    2014-08-23

    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

  8. Functional genes of non-model arthropods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Technology and bioinformatics facilitate studies of non-model organisms, including pest insects and insect biological control agents. A cDNA library prepared from a laboratory-reared colony of Lygus lineolaris male nymphs identified sequences that appeared to have known functions or close homologues...

  9. The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence.

    PubMed

    Dorus, Steve; Gilbert, Sandra L; Forster, Michele L; Barndt, Robert J; Lahn, Bruce T

    2003-07-15

    Theories predict that the long-term survival of duplicated genes requires their functional diversification, which can be accomplished by either subfunctionalization (the partitioning of ancestral functions among duplicates) or neofunctionalization (the acquisition of novel function). Here, we characterize the CDY-related mammalian gene family, focusing on three aspects of its evolution: gene copy number, tissue expression profile and amino acid sequence. We show that the progenitor of this gene family arose de novo in the mammalian ancestor via domain accretion. This progenitor later duplicated to generate CDYL and CDYL2, two autosomal genes found in all extant mammals. Prior to human-mouse divergence (and perhaps preceding the eutherian radiation), a processed CDYL transcript retroposed onto the Y chromosome to create CDY, the Y-linked member of the family. In the simian lineage, CDY was retained and subsequently amplified on the Y. In non-simian mammals, however, CDY appears to have been lost. The retention of the Y-linked CDY genes in simians spurred the process of subfunctionalization and possibly neofunctionalization. Subfunctionalization is evidenced by the observation that simian CDYL and CDYL2 retained their somatic housekeeping transcripts but lost the spermatogenic transcripts to the newly arisen CDY. Neo-functionalization is suggested by the rapid evolution of the CDY protein sequence. Thus, the CDY-related family offers an instructive example of how duplicated genes undergo functional diversification in both expression profile and protein sequence. It also supports the previously postulated notion that there is a tendency for spermatogenic functions to transfer from autosomes to the Y chromosome. PMID:12837688

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

    PubMed Central

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

    2014-01-01

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

  11. Variation analysis of transcriptome changes reveals cochlear genes and their associated functions in cochlear susceptibility to acoustic overstimulation.

    PubMed

    Yang, Shuzhi; Cai, Qunfeng; Bard, Jonathan; Jamison, Jennifer; Wang, Jianmin; Yang, Weiping; Hu, Bo Hua

    2015-12-01

    Individual variation in the susceptibility of the auditory system to acoustic overstimulation has been well-documented at both the functional and structural levels. However, the molecular mechanism responsible for this variation is unclear. The current investigation was designed to examine the variation patterns of cochlear gene expression using RNA-seq data and to identify the genes with expression variation that increased following acoustic trauma. This study revealed that the constitutive expressions of cochlear genes displayed diverse levels of gene-specific variation. These variation patterns were altered by acoustic trauma; approximately one-third of the examined genes displayed marked increases in their expression variation. Bioinformatics analyses revealed that the genes that exhibited increased variation were functionally related to cell death, biomolecule metabolism, and membrane function. In contrast, the stable genes were primarily related to basic cellular processes, including protein and macromolecular syntheses and transport. There was no functional overlap between the stable and variable genes. Importantly, we demonstrated that glutamate metabolism is related to the variation in the functional response of the cochlea to acoustic overstimulation. Taken together, the results indicate that our analyses of the individual variations in transcriptome changes of cochlear genes provide important information for the identification of genes that potentially contribute to the generation of individual variation in cochlear responses to acoustic overstimulation. This article is part of a Special Issue entitled . PMID:26024952

  12. Relating Stomatal Conductance to Leaf Functional Traits

    PubMed Central

    Kröber, Wenzel; Plath, Isa; Heklau, Heike; Bruelheide, Helge

    2015-01-01

    Leaf functional traits are important because they reflect physiological functions, such as transpiration and carbon assimilation. In particular, morphological leaf traits have the potential to summarize plants strategies in terms of water use efficiency, growth pattern and nutrient use. The leaf economics spectrum (LES) is a recognized framework in functional plant ecology and reflects a gradient of increasing specific leaf area (SLA), leaf nitrogen, phosphorus and cation content, and decreasing leaf dry matter content (LDMC) and carbon nitrogen ratio (CN). The LES describes different strategies ranging from that of short-lived leaves with high photosynthetic capacity per leaf mass to long-lived leaves with low mass-based carbon assimilation rates. However, traits that are not included in the LES might provide additional information on the species' physiology, such as those related to stomatal control. Protocols are presented for a wide range of leaf functional traits, including traits of the LES, but also traits that are independent of the LES. In particular, a new method is introduced that relates the plants’ regulatory behavior in stomatal conductance to vapor pressure deficit. The resulting parameters of stomatal regulation can then be compared to the LES and other plant functional traits. The results show that functional leaf traits of the LES were also valid predictors for the parameters of stomatal regulation. For example, leaf carbon concentration was positively related to the vapor pressure deficit (vpd) at the point of inflection and the maximum of the conductance-vpd curve. However, traits that are not included in the LES added information in explaining parameters of stomatal control: the vpd at the point of inflection of the conductance-vpd curve was lower for species with higher stomatal density and higher stomatal index. Overall, stomata and vein traits were more powerful predictors for explaining stomatal regulation than traits used in the LES. PMID:26484692

  13. Relating Stomatal Conductance to Leaf Functional Traits.

    PubMed

    Kröber, Wenzel; Plath, Isa; Heklau, Heike; Bruelheide, Helge

    2015-01-01

    Leaf functional traits are important because they reflect physiological functions, such as transpiration and carbon assimilation. In particular, morphological leaf traits have the potential to summarize plants strategies in terms of water use efficiency, growth pattern and nutrient use. The leaf economics spectrum (LES) is a recognized framework in functional plant ecology and reflects a gradient of increasing specific leaf area (SLA), leaf nitrogen, phosphorus and cation content, and decreasing leaf dry matter content (LDMC) and carbon nitrogen ratio (CN). The LES describes different strategies ranging from that of short-lived leaves with high photosynthetic capacity per leaf mass to long-lived leaves with low mass-based carbon assimilation rates. However, traits that are not included in the LES might provide additional information on the species' physiology, such as those related to stomatal control. Protocols are presented for a wide range of leaf functional traits, including traits of the LES, but also traits that are independent of the LES. In particular, a new method is introduced that relates the plants' regulatory behavior in stomatal conductance to vapor pressure deficit. The resulting parameters of stomatal regulation can then be compared to the LES and other plant functional traits. The results show that functional leaf traits of the LES were also valid predictors for the parameters of stomatal regulation. For example, leaf carbon concentration was positively related to the vapor pressure deficit (vpd) at the point of inflection and the maximum of the conductance-vpd curve. However, traits that are not included in the LES added information in explaining parameters of stomatal control: the vpd at the point of inflection of the conductance-vpd curve was lower for species with higher stomatal density and higher stomatal index. Overall, stomata and vein traits were more powerful predictors for explaining stomatal regulation than traits used in the LES. PMID:26484692

  14. The prediction of candidate genes for cervix related cancer through gene ontology and graph theoretical approach.

    PubMed

    Hindumathi, V; Kranthi, T; Rao, S B; Manimaran, P

    2014-06-01

    With rapidly changing technology, prediction of candidate genes has become an indispensable task in recent years mainly in the field of biological research. The empirical methods for candidate gene prioritization that succors to explore the potential pathway between genetic determinants and complex diseases are highly cumbersome and labor intensive. In such a scenario predicting potential targets for a disease state through in silico approaches are of researcher's interest. The prodigious availability of protein interaction data coupled with gene annotation renders an ease in the accurate determination of disease specific candidate genes. In our work we have prioritized the cervix related cancer candidate genes by employing Csaba Ortutay and his co-workers approach of identifying the candidate genes through graph theoretical centrality measures and gene ontology. With the advantage of the human protein interaction data, cervical cancer gene sets and the ontological terms, we were able to predict 15 novel candidates for cervical carcinogenesis. The disease relevance of the anticipated candidate genes was corroborated through a literature survey. Also the presence of the drugs for these candidates was detected through Therapeutic Target Database (TTD) and DrugMap Central (DMC) which affirms that they may be endowed as potential drug targets for cervical cancer. PMID:24647578

  15. Age-related macular degeneration: Evidence of a major gene

    SciTech Connect

    Bhatt, S.; Warren, C.; Yang, H.

    1994-09-01

    Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

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

    PubMed Central

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

    2015-01-01

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

  17. Structure-function relations are subtle in genetic regulatory networks.

    PubMed

    Wall, Michael E

    2011-05-01

    Recent studies have yielded insights into structure-function relations in genetic regulatory networks. Models of feed-forward loops show that the input-output behavior depends critically on the input signal as well as transcription interactions. Models of induction of the lac operon in Escherichia coli reveal the importance of metabolism in determining genetic regulatory network behavior. Combined experimental and computational studies of activation by MarA in E. coli show how mechanisms of transcription regulation, hidden at the level of genetic regulatory networks, can influence behavior. Together these studies illustrate that gene regulation is critically influenced by factors beyond the topology of genetic regulatory interactions. Prediction of the specific information processing roles of gene circuits is more difficult than we would like, but it is still possible. Thinking about evolution of proteins and networks might make it easier. PMID:21329703

  18. Loss of gene function and evolution of human phenotypes.

    PubMed

    Oh, Hye Ji; Choi, Dongjin; Goh, Chul Jun; Hahn, Yoonsoo

    2015-07-01

    Humans have acquired many distinct evolutionary traits after the human-chimpanzee divergence. These phenotypes have resulted from genetic changes that occurred in the human genome and were retained by natural selection. Comparative primate genome analyses reveal that loss-of-function mutations are common in the human genome. Some of these gene inactivation events were revealed to be associated with the emergence of advantageous phenotypes and were therefore positively selected and fixed in modern humans (the "less-ismore" hypothesis). Representative cases of human gene inactivation and their functional implications are presented in this review. Functional studies of additional inactive genes will provide insight into the molecular mechanisms underlying acquisition of various human-specific traits. PMID:25887751

  19. Loss of gene function and evolution of human phenotypes

    PubMed Central

    Oh, Hye Ji; Choi, Dongjin; Goh, Chul Jun; Hahn, Yoonsoo

    2015-01-01

    Humans have acquired many distinct evolutionary traits after the human-chimpanzee divergence. These phenotypes have resulted from genetic changes that occurred in the human genome and were retained by natural selection. Comparative primate genome analyses reveal that loss-of-function mutations are common in the human genome. Some of these gene inactivation events were revealed to be associated with the emergence of advantageous phenotypes and were therefore positively selected and fixed in modern humans (the “less-ismore” hypothesis). Representative cases of human gene inactivation and their functional implications are presented in this review. Functional studies of additional inactive genes will provide insight into the molecular mechanisms underlying acquisition of various human-specific traits. [BMB Reports 2015; 48(7): 373-379] PMID:25887751

  20. X-linked intellectual disability related genes disrupted by balanced X-autosome translocations.

    PubMed

    Moysés-Oliveira, Mariana; Guilherme, Roberta Santos; Meloni, Vera Ayres; Di Battista, Adriana; de Mello, Claudia Berlim; Bragagnolo, Silvia; Moretti-Ferreira, Danilo; Kosyakova, Nadezda; Liehr, Thomas; Carvalheira, Gianna Maria; Melaragno, Maria Isabel

    2015-12-01

    Detailed molecular characterization of chromosomal rearrangements involving X-chromosome has been a key strategy in identifying X-linked intellectual disability-causing genes. We fine-mapped the breakpoints in four women with balanced X-autosome translocations and variable phenotypes, in order to investigate the corresponding genetic contribution to intellectual disability. We addressed the impact of the gene interruptions in transcription and discussed the consequences of their functional impairment in neurodevelopment. Three patients presented with cognitive impairment, reinforcing the association between the disrupted genes (TSPAN7-MRX58, KIAA2022-MRX98, and IL1RAPL1-MRX21/34) and intellectual disability. While gene expression analysis showed absence of TSPAN7 and KIAA2022 expression in the patients, the unexpected expression of IL1RAPL1 suggested a fusion transcript ZNF611-IL1RAPL1 under the control of the ZNF611 promoter, gene disrupted at the autosomal breakpoint. The X-chromosomal breakpoint definition in the fourth patient, a woman with normal intellectual abilities, revealed disruption of the ZDHHC15 gene (MRX91). The expression assays did not detect ZDHHC15 gene expression in the patient, thus questioning its involvement in intellectual disability. Revealing the disruption of an X-linked intellectual disability-related gene in patients with balanced X-autosome translocation is a useful tool for a better characterization of critical genes in neurodevelopment. © 2015 Wiley Periodicals, Inc. PMID:26290131

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

    PubMed Central

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

    2014-01-01

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

  2. Cost-benefit theory and optimal design of gene regulation functions.

    PubMed

    Kalisky, Tomer; Dekel, Erez; Alon, Uri

    2007-11-01

    Cells respond to the environment by regulating the expression of genes according to environmental signals. The relation between the input signal level and the expression of the gene is called the gene regulation function. It is of interest to understand the shape of a gene regulation function in terms of the environment in which it has evolved and the basic constraints of biological systems. Here we address this by presenting a cost-benefit theory for gene regulation functions that takes into account temporally varying inputs in the environment and stochastic noise in the biological components. We apply this theory to the well-studied lac operon of E. coli. The present theory explains the shape of this regulation function in terms of temporal variation of the input signals, and of minimizing the deleterious effect of cell-cell variability in regulatory protein levels. We also apply the theory to understand the evolutionary tradeoffs in setting the number of regulatory proteins and for selection of feed-forward loops in genetic circuits. The present cost-benefit theory can be used to understand the shape of other gene regulatory functions in terms of environment and noise constraints. PMID:17991990

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

    PubMed Central

    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

    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

  4. Detecting Horizontal Gene Transfer between Closely Related Taxa

    PubMed Central

    Adato, Orit; Ninyo, Noga; Gophna, Uri; Snir, Sagi

    2015-01-01

    Horizontal gene transfer (HGT), the transfer of genetic material between organisms, is crucial for genetic innovation and the evolution of genome architecture. Existing HGT detection algorithms rely on a strong phylogenetic signal distinguishing the transferred sequence from ancestral (vertically derived) genes in its recipient genome. Detecting HGT between closely related species or strains is challenging, as the phylogenetic signal is usually weak and the nucleotide composition is normally nearly identical. Nevertheless, there is a great importance in detecting HGT between congeneric species or strains, especially in clinical microbiology, where understanding the emergence of new virulent and drug-resistant strains is crucial, and often time-sensitive. We developed a novel, self-contained technique named Near HGT, based on the synteny index, to measure the divergence of a gene from its native genomic environment and used it to identify candidate HGT events between closely related strains. The method confirms candidate transferred genes based on the constant relative mutability (CRM). Using CRM, the algorithm assigns a confidence score based on “unusual” sequence divergence. A gene exhibiting exceptional deviations according to both synteny and mutability criteria, is considered a validated HGT product. We first employed the technique to a set of three E. coli strains and detected several highly probable horizontally acquired genes. We then compared the method to existing HGT detection tools using a larger strain data set. When combined with additional approaches our new algorithm provides richer picture and brings us closer to the goal of detecting all newly acquired genes in a particular strain. PMID:26439115

  5. Detecting Horizontal Gene Transfer between Closely Related Taxa.

    PubMed

    Adato, Orit; Ninyo, Noga; Gophna, Uri; Snir, Sagi

    2015-10-01

    Horizontal gene transfer (HGT), the transfer of genetic material between organisms, is crucial for genetic innovation and the evolution of genome architecture. Existing HGT detection algorithms rely on a strong phylogenetic signal distinguishing the transferred sequence from ancestral (vertically derived) genes in its recipient genome. Detecting HGT between closely related species or strains is challenging, as the phylogenetic signal is usually weak and the nucleotide composition is normally nearly identical. Nevertheless, there is a great importance in detecting HGT between congeneric species or strains, especially in clinical microbiology, where understanding the emergence of new virulent and drug-resistant strains is crucial, and often time-sensitive. We developed a novel, self-contained technique named Near HGT, based on the synteny index, to measure the divergence of a gene from its native genomic environment and used it to identify candidate HGT events between closely related strains. The method confirms candidate transferred genes based on the constant relative mutability (CRM). Using CRM, the algorithm assigns a confidence score based on "unusual" sequence divergence. A gene exhibiting exceptional deviations according to both synteny and mutability criteria, is considered a validated HGT product. We first employed the technique to a set of three E. coli strains and detected several highly probable horizontally acquired genes. We then compared the method to existing HGT detection tools using a larger strain data set. When combined with additional approaches our new algorithm provides richer picture and brings us closer to the goal of detecting all newly acquired genes in a particular strain. PMID:26439115

  6. Tandem riboswitch architectures exhibit complex gene control functions.

    PubMed

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

    2006-10-13

    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

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

    SciTech Connect

    V, DE CRECY-LAGARD; D, HANSON A

    2012-01-03

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

  8. COMT gene locus: new functional variants.

    PubMed

    Meloto, Carolina B; Segall, Samantha K; Smith, Shad; Parisien, Marc; Shabalina, Svetlana A; Rizzatti-Barbosa, Célia M; Gauthier, Josée; Tsao, Douglas; Convertino, Marino; Piltonen, Marjo H; Slade, Gary Dmitri; Fillingim, Roger B; Greenspan, Joel D; Ohrbach, Richard; Knott, Charles; Maixner, William; Zaykin, Dmitri; Dokholyan, Nikolay V; Reenilä, Ilkka; Männistö, Pekka T; Diatchenko, Luda

    2015-10-01

    Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways. Here, we show that association studies between COMT polymorphic markers and pain phenotypes in 2 independent cohorts identified a functional marker, rs165774, situated in the 3' untranslated region of a newfound splice variant, (a)-COMT. Sequence comparisons showed that the (a)-COMT transcript is highly conserved in primates, and deep sequencing data demonstrated that (a)-COMT is expressed across several human tissues, including the brain. In silico analyses showed that the (a)-COMT enzyme features a distinct C-terminus structure, capable of stabilizing substrates in its active site. In vitro experiments demonstrated not only that (a)-COMT is catalytically active but also that it displays unique substrate specificity, exhibiting enzymatic activity with dopamine but not epinephrine. They also established that the pain-protective A allele of rs165774 coincides with lower COMT activity, suggesting contribution to decreased pain sensitivity through increased dopaminergic rather than decreased adrenergic tone, characteristic of reference isoforms. Our results provide evidence for an essential role of the (a)-COMT isoform in nociceptive signaling and suggest that genetic variations in (a)-COMT isoforms may contribute to individual variability in pain phenotypes. PMID:26207649

  9. Gene-environment interactions of circadian-related genes for cardiometabolic traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs1...

  10. 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...

  11. ORIGINAL ARTICLE Discovery and replication of dopamine-related gene

    E-print Network

    Thompson, Paul

    ORIGINAL ARTICLE Discovery and replication of dopamine-related gene effects on caudate volume Francisco, CA, USA The caudate is a subcortical brain structure implicated in many common neurological's Disease NeuroImaging Initiative (ADNI; N = 734) and the Brisbane Adolescent/Young Adult Longitudinal Twin

  12. APOLIPOPROTEIN E GENE AND EARLY AGE-RELATED MACULOPATHY

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2015-02-01

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

  14. New gene functions in megakaryopoiesis and platelet formation.

    PubMed

    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

    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

  15. New gene functions in megakaryopoiesis and platelet formation

    PubMed Central

    Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O’Reilly, Paul F.; Shin, So-Youn; Esko, 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

    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

  16. Gene annotation and functional analysis of a newly sequenced Synechococcus strain.

    PubMed

    Li, Y; Rao, N N; Yang, Y; Zhang, Y; Gu, Y N

    2015-01-01

    Synechococcus sp PCC 7336 represents a newly sequenced strain, and its genome is obviously different from that of other Synechococcus strains. In this analysis, local alignment and annotation databases were constructed and combined with various bioinformatic tools to carry out gene annotation and functional analysis of this strain. From this analysis, we identified 5096 protein-coding genes and 47 RNA genes. Of these, 116 genes that were classified into 9 categories were associated with photosynthesis, and type V polymerase proteins that were identified are unique for this strain. An additional 107 genes were closely related to signal transduction pathways, which primarily comprised parts of two-component regulatory systems. Gene ontogeny analysis showed that 2377 genes were annotated with a total number of 9791 functional categories, and specifically that 41 genes distributed in 4 protein complexes were involved in oxidative phosphorylation. Clusters of orthologous groups classification showed that there were 1463 homologous proteins associated with 17 specific metabolic pathways, and that most of the proteins participated in primary metabolic processes such as binding and catalysis. The phylogenetic tree based on 16S rRNA sequences indicated that Synechococcus PCC 7336 is highly likely to represent a new branch. PMID:26505391

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

    PubMed Central

    Gao, Xiquan; Shan, Libo

    2015-01-01

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

  18. Turkey fecal microbial community structure and functional gene diversity revealed by 16S rRNA gene and metagenomic sequences.

    PubMed

    Lu, Jingrang; Domingo, Jorge Santo

    2008-10-01

    The primary goal of this study was to better understand the microbial composition and functional genetic diversity associated with turkey fecal communities. To achieve this, 16S rRNA gene and metagenomic clone libraries were sequenced from turkey fecal samples. The analysis of 382 16S rRNA gene sequences showed that the most abundant bacteria were closely related to Lactobacillales (47%), Bacillales (31%), and Clostridiales (11%). Actinomycetales, Enterobacteriales, and Bacteroidales sequences were also identified, but represented a smaller part of the community. The analysis of 379 metagenomic sequences showed that most clones were similar to bacterial protein sequences (58%). Bacteriophage (10%) and avian viruses (3%) sequences were also represented. Of all metagenomic clones potentially encoding for bacterial proteins, most were similar to low G+C Gram-positive bacterial proteins, particularly from Lactobacillales (50%), Bacillales (11%), and Clostridiales (8%). Bioinformatic analyses suggested the presence of genes encoding for membrane proteins, lipoproteins, hydrolases, and functional genes associated with the metabolism of nitrogen and sulfur containing compounds. The results from this study further confirmed the predominance of Firmicutes in the avian gut and highlight the value of coupling 16S rRNA gene and metagenomic sequencing data analysis to study the microbial composition of avian fecal microbial communities. PMID:18974945

  19. Penetrance of pathogenic mutations in haploinsufficient genes for intellectual disability and related disorders.

    PubMed

    Ropers, H Hilger; Wienker, Thomas

    2015-12-01

    De novo loss of function (LOF) mutations in the ASXL3 gene cause Bainbridge-Ropers syndrome, a severe form of intellectual disability (ID) and developmental delay, but there is evidence that they also occur in healthy individuals. This has prompted us to look for non-pathogenic LOF variants in other ID genes. Heterozygous LOF mutations in ASXL1, a paralog of ASXL3, are known to cause Bohring-Opitz syndrome (BOS), and benign LOF mutations in this gene have not been published to date. Therefore, we were surprised to find 56 ASXL1 LOF variants in the ExAC database (http://exac.broadinstitute.org), comprising exomes from 60,706 individuals who had been selected to exclude severe genetic childhood disorders. 4 of these variants have been described as disease-causing in patients with BOS, which rules out the possibility that pathogenic and clinically neutral LOF variants in this gene are functionally distinct. Apparently benign LOF variants were also detected in several other genes for ID and related disorders, including CDH15, KATNAL2, DEPDC5, ARID1B and AUTS2, both in the ExAC database and in the 6,500 exomes of the Exome Variant Server (http://evs.gs.washington.edu/EVS/). These observations argue for low penetrance of LOF mutations in ASXL1 and other genes for ID and related disorders, which could have far-reaching implications for genetic counseling and research. PMID:26506440

  20. Gene fusions and gene duplications: relevance to genomic annotation and functional analysis

    PubMed Central

    Serres, Margrethe H; Riley, Monica

    2005-01-01

    Background Escherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular) proteins consist of two or more components (modules) encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work overstated the number of multimodular proteins in E. coli. This work corrects the identification of modules by including sequence information from proteins in 50 sequenced microbial genomes. Results Multimodular E. coli K-12 proteins were identified from sequence similarities between their component modules and non-fused proteins in 50 genomes and from the literature. We found 109 multimodular proteins in E. coli containing either two or three modules. Most modules had standalone sequence relatives in other genomes. The separated modules together with all the single (un-fused) proteins constitute the sum of all unimodular proteins of E. coli. Pairwise sequence relationships among all E. coli unimodular proteins generated 490 sequence similar, paralogous groups. Groups ranged in size from 92 to 2 members and had varying degrees of relatedness among their members. Some E. coli enzyme groups were compared to homologs in other bacterial genomes. Conclusion The deleterious effects of multimodular proteins on annotation and on the formation of groups of paralogs are emphasized. To improve annotation results, all multimodular proteins in an organism should be detected and when known each function should be connected with its location in the sequence of the protein. When transferring functions by sequence similarity, alignment locations must be noted, particularly when alignments cover only part of the sequences, in order to enable transfer of the correct function. Separating multimodular proteins into module units makes it possible to generate protein groups related by both sequence and function, avoiding mixing of unrelated sequences. Organisms differ in sizes of groups of sequence-related proteins. A sample comparison of orthologs to selected E. coli paralogous groups correlates with known physiological and taxonomic relationships between the organisms. PMID:15757509

  1. Systems-wide chicken DNA microarrays, gene expression profiling, and discovery of functional genes.

    PubMed

    Cogburn, L A; Wang, X; Carre, W; Rejto, L; Porter, T E; Aggrey, S E; Simon, J

    2003-06-01

    The goal of our current consortium project is to launch a new era--functional genomics of poultry--by providing genomic resources [expressed sequence tags (EST) and DNA microarrays] and by examining global gene expression in target tissues of chickens. DNA microarray analysis has been a fruitful strategy for the identification of functional genes in several model organisms (i.e., human, rodents, fruit fly, etc.). We have constructed and normalized five tissue-specific or multiple-tissue chicken cDNA libraries [liver, fat, breast, and leg muscle/epiphyseal growth plate, pituitary/hypothalamus/pineal, and reproductive tract (oviduct/ovary/testes)] for high-throughput DNA sequencing of EST. DNA sequence clustering was used to build contigs of overlapping sequence and to identify unique, non-redundant EST clones (unigenes), which permitted printing of systems-wide chicken DNA microarrays. One of the most promising genetic resources for gene exploration and functional gene mapping is provided by two sets of experimental lines of broiler-type chickens developed at INRA, France, by divergent selection for extremes in growth traits (fast-growing versus slow-growing; fatness versus leanness at a similar growth rate). We are using DNA microarrays for global gene expression profiling to identify candidate genes and to map growth, metabolic, and regulatory pathways that control important production traits. Candidate genes will be used for functional gene mapping and QTL analysis of F2 progeny from intercrosses made between divergent genetic lines (fat x lean lines; fast-growing x slow-growing lines). Using our first chicken liver microarray, we have already identified several interesting differentially expressed genes in commercial broilers and in divergently selected broiler lines. Many of these candidate genes are involved in the lipogenic pathway and are controlled in part by the thyrotropic axis. Thus, genome-wide transcriptional profiling is a powerful tool used to visualize the cascade of genetic circuits that govern complex biological responses. Global gene expression profiling and QTL scans should enable us to functionally map the genetic pathways that control growth, development, and metabolism of chickens. This emerging technology will have broad applications for poultry breeding programs (i.e., use of molecular markers) and for future production systems (i.e., the health and welfare of birds and the quality of poultry products). PMID:12817449

  2. 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

  3. Multiple Functions of a Feed-Forward-Loop Gene Circuit

    E-print Network

    Dunlop, Mary

    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

  4. Gene Fusion Technology NEW METHODS FOR ENHANCING FUNCTIONAL PROTEIN

    E-print Network

    Lebendiker, Mario

    SUMOpro® Gene Fusion Technology NEW METHODS FOR ENHANCING FUNCTIONAL PROTEIN EXPRESSION packed globular fold with -sheets wrapped around an -helix. Smt3 Fusions Yeast SUMO (Smt3) fused (ubiquitin or SUMO) at the N-terminus of a partner protein increases the recombinant fusion protein yield

  5. Gene Fusion Technology NEW METHODS FOR ENHANCING FUNCTIONAL PROTEIN

    E-print Network

    Lebendiker, Mario

    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

  6. Expression of mitochondria-related genes is elevated in overfeeding-induced goose fatty liver.

    PubMed

    Osman, Rashid H; Shao, Dan; Liu, Long; Xia, Lili; Sun, Xiaoxian; Zheng, Yun; Wang, Laidi; Zhang, Rui; Zhang, Yihui; Zhang, Jun; Gong, Daoqing; Geng, Tuoyu

    2016-02-01

    Mitochondrion, the power house of the cell, is an important organelle involving in energy homeostasis. Change in mitochondrial mass and function may lead to metabolic disorders. Previous studies indicate that mitochondrial mass loss and dysfunction are associated with non-alcoholic fatty liver disease (NAFLD) in human and mouse. However, it is unclear whether mitochondrial genes are involved in the development of goose fatty liver. To address this, we determined the response of goose mitochondrial genes to overfeeding and other fatty liver-related factors (e.g., hyperinsulinemia, hyperglycemia, and hyperlipidemia). We first employed RNA-seq technology to determine the differentially expressed genes in the livers from normally-fed vs. overfed geese, followed by bioinformatics analysis and quantitative PCR validation. Data indicated that a majority of mitochondrial genes in the liver were induced by overfeeding. To understand how these genes are regulated in the context of fatty liver, we treated goose primary hepatocytes with high levels of glucose, fatty acids and insulin. The results indicated that these factors had an influence on the expression of some mitochondria related genes. Together, these findings suggest that the induction of mitochondrial gene expression by overfeeding is required for the development of goose fatty liver, and this induction is partially attributable to hyperglycemia, hyperlipidemia and hyperinsulinemia. PMID:26627127

  7. Gene regulation by long purine tracks in brain related diseases.

    PubMed

    Singh, Himanshu Narayan; Rajeswari, Moganty R

    2015-12-01

    Purine repeats are randomly distributed in the human genome, however, they show potential role in the transcriptional deregulation of genes. Presence of long tracks of purine repeats in the genome can disturb its integrity and interfere with the cellular behavior by introducing mutations and/or triple stranded structure formation in DNA. Our data revealed interesting finding that a majority of genes carrying purine repeats, of length n?200, were down regulated and found to be linked with several brain related diseases [1]. The unique feature of the purine repeats found in the present study clearly manifests their significant application in developing therapeutics for neurological diseases. PMID:26543885

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

    SciTech Connect

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

    2010-05-17

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

  9. Inferring functional transcription factor-gene binding pairs by integrating transcription factor binding data with transcription factor knockout data

    PubMed Central

    2013-01-01

    Background Chromatin immunoprecipitation (ChIP) experiments are now the most comprehensive experimental approaches for mapping the binding of transcription factors (TFs) to their target genes. However, ChIP data alone is insufficient for identifying functional binding target genes of TFs for two reasons. First, there is an inherent high false positive/negative rate in ChIP-chip or ChIP-seq experiments. Second, binding signals in the ChIP data do not necessarily imply functionality. Methods It is known that ChIP-chip data and TF knockout (TFKO) data reveal complementary information on gene regulation. While ChIP-chip data can provide TF-gene binding pairs, TFKO data can provide TF-gene regulation pairs. Therefore, we propose a novel network approach for identifying functional TF-gene binding pairs by integrating the ChIP-chip data with the TFKO data. In our method, a TF-gene binding pair from the ChIP-chip data is regarded to be functional if it also has high confident curated TFKO TF-gene regulatory relation or deduced hypostatic TF-gene regulatory relation. Results and conclusions We first validated our method on a gathered ground truth set. Then we applied our method to the ChIP-chip data to identify functional TF-gene binding pairs. The biological significance of our identified functional TF-gene binding pairs was shown by assessing their functional enrichment, the prevalence of protein-protein interaction, and expression coherence. Our results outperformed the results of three existing methods across all measures. And our identified functional targets of TFs also showed statistical significance over the randomly assigned TF-gene pairs. We also showed that our method is dataset independent and can apply to ChIP-seq data and the E. coli genome. Finally, we provided an example showing the biological applicability of our notion. PMID:24565265

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

    SciTech Connect

    Efrose, Rodica; Swevers, Luc; Iatrou, Kostas

    2010-10-25

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

  11. The Spatial Distribution of Nitrogen Removal Functional Genes in Multimedia Constructed Wetlands for Wastewater Treatment.

    PubMed

    Ji, Guodong; He, Chunguang; Tan, Yufei; Yang, Zhonghua

    2015-11-01

    The real-time polymerase chain reaction was used to quantitatively evaluate distribution patterns and nitrogen removal pathways of the amoA, nxrA, narG, napA, nirK, qnorB, nosZ, nas, and nifH genes and 16S rRNA in anaerobic ammonia oxidation bacteria in four multimedia constructed wetlands for rural wastewater treatment. The results indicated that the abundance of functional genes for nitrogen removal in the rhizosphere layer (0 to 30 cm), water distribution layer (30 to 50 cm), multime filler layer (50 to 130 cm), and catchment layer (130 to170 cm) of the constructed wetlands were closely related. The rhizosphere layer was conducive to the absolute enrichment of dominant genes. The other three layers were favorable to the relative enrichment of rare genes. PMID:26564582

  12. Towards the Discovery of Diseases Related by Genes Using Vertex Similarity Measures

    E-print Network

    Giles, C. Lee

    Towards the Discovery of Diseases Related by Genes Using Vertex Similarity Measures Hung-Hsuan Chen--Discovering the relationships of gene to gene, gene to its related diseases, and diseases implicated in common genes is important. However, traditional biological methods can be expensive. Here, we show that the diseases

  13. Functional Annotation of Genes Overlapping Copy Number Variants in Autistic Patients: Focus on Axon Pathfinding

    PubMed Central

    Sbacchi, Silvia; Acquadro, Francesco; Calò, Ignazio; Calì, Francesco; Romano, Valentino

    2010-01-01

    We have used Gene Ontology (GO) and pathway analyses to uncover the common functions associated to the genes overlapping Copy Number Variants (CNVs) in autistic patients. Our source of data were four published studies [1-4]. We first applied a two-step enrichment strategy for autism-specific genes. We fished out from the four mentioned studies a list of 2928 genes overall overlapping 328 CNVs in patients and we first selected a sub-group of 2044 genes after excluding those ones that are also involved in CNVs reported in the Database of Genomic Variants (enrichment step 1). We then selected from the step 1-enriched list a sub-group of 514 genes each of which was found to be deleted or duplicated in at least two patients (enrichment step 2). The number of statistically significant processes and pathways identified by the Database for Annotation, Visualization and Integrated Discovery and Ingenuity Pathways Analysis softwares with the step 2-enriched list was significantly higher compared to the step 1-enriched list. In addition, statistically significant GO terms, biofunctions and pathways related to nervous system development and function were exclusively identified by the step 2-enriched list of genes. Interestingly, 21 genes were associated to axon growth and pathfinding. The latter genes and other ones associated to nervous system in this study represent a new set of autism candidate genes deserving further investigation. In summary, our results suggest that the autism’s “connectivity genes” in some patients affect very early phases of neurodevelopment, i.e., earlier than synaptogenesis. PMID:20885821

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

    PubMed Central

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

    2015-01-01

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

  15. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

    PubMed Central

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

    2014-01-01

    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

  16. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    PubMed Central

    Ragazzo, Michele; Missiroli, Filippo; Borgiani, Paola; Angelucci, Francesco; Marsella, Luigi Tonino; Cusumano, Andrea; Novelli, Giuseppe; Ricci, Federico; Giardina, Emiliano

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression. PMID:25478207

  17. Gene-Diet Interactions in Age-Related Macular Degeneration.

    PubMed

    Rowan, Sheldon; Taylor, Allen

    2016-01-01

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50 % of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation is the only available treatment option for the dry form of the disease known to slow progression of AMD. Despite an excellent understanding of genes and nutrition in AMD, there is remarkably little known about gene-diet interactions that may identify efficacious approaches to treat individuals. This review will summarize our current understanding of gene-diet interactions in AMD with a focus on animal models and human epidemiological studies. PMID:26427399

  18. Mutations in human monoamine-related neurotransmitter pathway genes.

    PubMed

    Haavik, Jan; Blau, Nenad; Thöny, Beat

    2008-07-01

    Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DbetaH), and phenylethanolamine N-methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O-methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org). PMID:18444257

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

    PubMed Central

    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

    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

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

    PubMed Central

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

    2015-01-01

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

  1. Structure and function of pseudoknots involved in gene expression control

    PubMed Central

    Peselis, Alla; Serganov, Alexander

    2015-01-01

    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 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

  2. Identification of apoptosis-related PLZF target genes

    SciTech Connect

    Bernardo, Maria Victoria; Yelo, Estefania; Gimeno, Lourdes; Campillo, Jose Antonio; Parrado, Antonio . E-mail: antonio.parrado@carm.es

    2007-07-27

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

  3. Interspecies Variations in Bordetella Catecholamine Receptor Gene Regulation and Function.

    PubMed

    Brickman, Timothy J; Suhadolc, Ryan J; Armstrong, Sandra K

    2015-12-01

    Bordetella bronchiseptica can use catecholamines to obtain iron from transferrin and lactoferrin via uptake pathways involving the BfrA, BfrD, and BfrE outer membrane receptor proteins, and although Bordetella pertussis has the bfrD and bfrE genes, the role of these genes in iron uptake has not been demonstrated. In this study, the bfrD and bfrE genes of B. pertussis were shown to be functional in B. bronchiseptica, but neither B. bronchiseptica bfrD nor bfrE imparted catecholamine utilization to B. pertussis. Gene fusion analyses found that expression of B. bronchiseptica bfrA was increased during iron starvation, as is common for iron receptor genes, but that expression of the bfrD and bfrE genes of both species was decreased during iron limitation. As shown previously for B. pertussis, bfrD expression in B. bronchiseptica was also dependent on the BvgAS virulence regulatory system; however, in contrast to the case in B. pertussis, the known modulators nicotinic acid and sulfate, which silence Bvg-activated genes, did not silence expression of bfrD in B. bronchiseptica. Further studies using a B. bronchiseptica bvgAS mutant expressing the B. pertussis bvgAS genes revealed that the interspecies differences in bfrD modulation are partly due to BvgAS differences. Mouse respiratory infection experiments determined that catecholamine utilization contributes to the in vivo fitness of B. bronchiseptica and B. pertussis. Additional evidence of the in vivo importance of the B. pertussis receptors was obtained from serologic studies demonstrating pertussis patient serum reactivity with the B. pertussis BfrD and BfrE proteins. PMID:26371128

  4. Functional Studies of Regulatory Genes in the Sea Urchin Embryo

    NASA Astrophysics Data System (ADS)

    Cavalieri, Vincenzo; Bernardo, Maria Di; Spinelli, Giovanni

    Sea urchin embryos are characterized by an extremely simple mode of development, rapid cleavage, high transparency, and well-defined cell lineage. Although they are not suitable for genetic studies, other approaches are successfully used to unravel mechanisms and molecules involved in cell fate specification and morphogenesis. Microinjection is the elective method to study gene function in sea urchin embryos. It is used to deliver precise amounts of DNA, RNA, oligonucleotides, peptides, or antibodies into the eggs or even into blastomeres. Here we describe microinjection as it is currently applied in our laboratory and show how it has been used in gene perturbation analyses and dissection of cis-regulatory DNA elements.

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

    PubMed Central

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

    2011-01-01

    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

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

    PubMed

    Shimizu, Takeo; Ito, Tsutae; Kanematsu, Satoko

    2014-04-01

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

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

    PubMed Central

    Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; 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.

    2013-01-01

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

  8. Bioinformatic analysis of cancer-related microRNAs and their target genes.

    PubMed

    Xue, Zhou; Yilan, Du; Ping, Jin; Fei, Ma

    2015-09-01

    MicroRNAs (miRNAs) are a class of ?22 nucleotide endogenous noncoding RNAs which regulate gene expression by targeting complementary transcripts. Recent studies have found that miRNAs are closely related to tumorigenesis and can act as oncogenes or tumor suppressor genes to influence the occurrence and development of tumor. To further reveal characteristics of cancer-related miRNAs and the functions of miRNA targets, we obtained 475 miRNAs involved in cancer through database searching and information retrieval. We systematically analyzed and compared the features including conservation, SNP distribution, cancer spectrum width, and transcriptional regulation between cancer and non-cancer related miRNAs as well as between intergenic and intragenic miRNAs. Our results showed that cancer-related miRNAs have higher conservation and lower SNP frequency compared to non-cancer-related miRNAs, and the cancer spectrum of one miRNA is positively correlated with its conservation. Genome analysis showed that cancer-related miRNAs tend to present as clusters compared with non-cancer-related miRNAs. Further association analysis between cancer progression and host genes, cancer-related miRNAs or target genes found that the host genes of some non-cancer related miRNAs tend to be targeted by cancer-related miRNAs. This study provides theoretical basis for further understanding the relationship between miRNA and cancer progression as well as the miRNA-based cancer diagnosis. PMID:26399525

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

    PubMed Central

    Noble, Luke M.; Andrianopoulos, Alex

    2013-01-01

    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

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

    PubMed Central

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

    1996-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

  12. The functional gene composition and metabolic potential of coral-associated microbial communities.

    PubMed

    Zhang, Yanying; Ling, Juan; Yang, Qingsong; Wen, Chongqing; Yan, Qingyun; Sun, Hongyan; Van Nostrand, Joy D; Shi, Zhou; Zhou, Jizhong; Dong, Junde

    2015-01-01

    The phylogenetic diversity of coral-associated microbes has been extensively examined, but some contention remains regarding whether coral-associated microbial communities are species-specific or site-specific. It is suggested that corals may associate with microbes in terms of function, although little is known about the differences in coral-associated microbial functional gene composition and metabolic potential among coral species. Here, 16S rRNA Illumina sequencing and functional gene array (GeoChip 5.0) were used to assess coral-associated microbial communities. Our results indicate that both host species and environmental variables significantly correlate with shifts in the microbial community structure and functional potential. Functional genes related to key biogeochemical cycles including carbon, nitrogen, sulfur and phosphorus cycling, metal homeostasis, organic remediation, antibiotic resistance and secondary metabolism were shown to significantly vary between and among the four study corals (Galaxea astreata, Porites lutea, Porites andrewsi and Pavona decussata). Genes specific for anammox were also detected for the first time in the coral holobiont and positively correlated with ammonium. This study reveals that variability in the functional potential of coral-associated microbial communities is largely driven by changes in environmental factors and further demonstrates the importance of linking environmental parameters with genomic data in complex environmental systems. PMID:26536917

  13. The functional gene composition and metabolic potential of coral-associated microbial communities

    PubMed Central

    Zhang, Yanying; Ling, Juan; Yang, Qingsong; Wen, Chongqing; Yan, Qingyun; Sun, Hongyan; Van Nostrand, Joy D.; Shi, Zhou; Zhou, Jizhong; Dong, Junde

    2015-01-01

    The phylogenetic diversity of coral-associated microbes has been extensively examined, but some contention remains regarding whether coral-associated microbial communities are species-specific or site-specific. It is suggested that corals may associate with microbes in terms of function, although little is known about the differences in coral-associated microbial functional gene composition and metabolic potential among coral species. Here, 16S rRNA Illumina sequencing and functional gene array (GeoChip 5.0) were used to assess coral-associated microbial communities. Our results indicate that both host species and environmental variables significantly correlate with shifts in the microbial community structure and functional potential. Functional genes related to key biogeochemical cycles including carbon, nitrogen, sulfur and phosphorus cycling, metal homeostasis, organic remediation, antibiotic resistance and secondary metabolism were shown to significantly vary between and among the four study corals (Galaxea astreata, Porites lutea, Porites andrewsi and Pavona decussata). Genes specific for anammox were also detected for the first time in the coral holobiont and positively correlated with ammonium. This study reveals that variability in the functional potential of coral-associated microbial communities is largely driven by changes in environmental factors and further demonstrates the importance of linking environmental parameters with genomic data in complex environmental systems. PMID:26536917

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

    SciTech Connect

    Reeve, Jennifer; Schadt, Christopher Warren; Carpenter-Boggs, Lynne; Kang, S.; Zhou, Jizhong; Reganold, John P.

    2010-01-01

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

  15. Transcriptional regulation of genes related to progesterone production [Review].

    PubMed

    Mizutani, Tetsuya; Ishikane, Shin; Kawabe, Shinya; Umezawa, Akihiro; Miyamoto, Kaoru

    2015-09-30

    Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3?-hydroxysteroid dehydrogenase/?(5)-?(4) isomerase (3?-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert ?(5)-?(4) isomerization activity to produce progesterone in a cooperative fashion with 3?-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production. PMID:26135521

  16. 'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism.

    PubMed

    Wang, Zhengfei; Chen, Zhuo; Xu, Shixia; Ren, Wenhua; Zhou, Kaiya; Yang, Guang

    2015-01-01

    Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans. PMID:26381091

  17. ‘Obesity’ is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism

    PubMed Central

    Wang, Zhengfei; Chen, Zhuo; Xu, Shixia; Ren, Wenhua; Zhou, Kaiya; Yang, Guang

    2015-01-01

    Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that ‘obesity’ might be an indicator of good health for cetaceans. PMID:26381091

  18. Molecular Analysis of a Family of Arabidopsis Genes Related to Galacturonosyltransferases1[W][OA

    PubMed Central

    Kong, Yingzhen; Zhou, Gongke; Yin, Yanbin; Xu, Ying; Pattathil, Sivakumar; Hahn, Michael G.

    2011-01-01

    We are studying a Galacturonosyltransferase-Like (GATL) gene family in Arabidopsis (Arabidopsis thaliana) that was identified bioinformatically as being closely related to a group of 15 genes (Galacturonosyltransferase1 [GAUT1] to -15), one of which (GAUT1) has been shown to encode a functional galacturonosyltransferase. Here, we describe the phylogeny, gene structure, evolutionary history, genomic organization, protein topology, and expression pattern of this gene family in Arabidopsis. Expression studies (reverse transcription-polymerase chain reaction) demonstrate that all 10 AtGATL genes are transcribed, albeit to varying degrees, in Arabidopsis tissues. Promoter::?-glucuronidase expression studies show that individual AtGATL gene family members have both overlapping and unique expression patterns. Nine of the 10 AtGATL genes are expressed in all major plant organs, although not always in all cell types of those organs. AtGATL4 expression appears to be confined to pollen grains. Most of the AtGATL genes are expressed strongly in vascular tissue in both the stem and hypocotyl. Subcellular localization studies of several GATL proteins using yellow fluorescent protein tagging provide evidence supporting the Golgi localization of these proteins. Plants carrying T-DNA insertions in three AtGATL genes (atgatl3, atgatl6, and atgatl9) have reduced amounts of GalA in their stem cell walls. The xylose content increased in atgatl3 and atgatl6 stem walls. Glycome profiling of cell wall fractions from these mutants using a toolkit of diverse plant glycan-directed monoclonal antibodies showed that the mutations affect both pectins and hemicelluloses and alter overall wall structure, as indicated by altered epitope extractability patterns. The data presented suggest that the AtGATL genes encode proteins involved in cell wall biosynthesis, but their precise roles in wall biosynthesis remain to be substantiated. PMID:21300919

  19. Comparison of lists of genes based on functional profiles

    PubMed Central

    2011-01-01

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

  20. Expression and interaction analysis of Arabidopsis Skp1-related genes.

    PubMed

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

    2004-01-01

    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

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

    PubMed Central

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

    2015-01-01

    MicroRNAs (miRNAs) are important regulators of gene expression and like any other gene, their coding sequences are subject to genetic variation. Variants in miRNA genes can have profound effects on miRNA functionality at all levels, including miRNA transcription, maturation, and target specificity, and as such they can also contribute to disease. The impact of variants in miRNA genes is the focus of the present review. To put these effects into context, we first discuss the requirements of miRNA transcripts for maturation. In the last part an overview of available databases and tools and experimental approaches to investigate miRNA variants related to human disease is presented. PMID:26052338

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

    PubMed Central

    2012-01-01

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

  3. Molecular cloning of allelopathy related genes and their relation to HHO in Eupatorium adenophorum.

    PubMed

    Guo, Huiming; Pei, Xixiang; Wan, Fanghao; Cheng, Hongmei

    2011-10-01

    In this study, conserved sequence regions of HMGR, DXR, and CHS (encoding 3-hydroxy-3-methylglutaryl-CoA reductase, 1-deoxyxylulose-5-phosphate reductoisomerase and chalcone synthase, respectively) were amplified by reverse transcriptase (RT)-PCR from Eupatorium adenophorum. Quantitative real-time PCR showed that the expression of CHS was related to the level of HHO, an allelochemical isolated from E. adenophorum. Semi-quantitative RT-PCR showed that there was no significant difference in expression of genes among three different tissues, except for CHS. Southern blotting indicated that at least three CHS genes are present in the E. adenophorum genome. A full-length cDNA from CHS genes (named EaCHS1, GenBank ID: FJ913888) was cloned. The 1,455 bp cDNA contained an open reading frame (1,206 bp) encoding a protein of 401 amino acids. Preliminary bioinformatics analysis of EaCHS1 revealed that EaCHS1 was a member of CHS family, the subcellular localization predicted that EaCHS1 was a cytoplasmic protein. To the best of our knowledge, this is the first report of conserved sequences of these genes and of a full-length EaCHS1 gene in E. adenophorum. The results indicated that CHS gene is related to allelopathy of E. adenophorum. PMID:21127986

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

    SciTech Connect

    Jaing, C

    2007-11-01

    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.

  5. Tenm, a Drosophila gene related to tenascin, is a new pair-rule gene.

    PubMed Central

    Baumgartner, S; Martin, D; Hagios, C; Chiquet-Ehrismann, R

    1994-01-01

    We describe the molecular characterization of the Drosophila gene tenm, a large transcription unit spanning > 110 kb of DNA. tenm encodes a large extracellular protein of 2515 amino acids related to the extracellular matrix molecule tenascin. The Tenm protein is found in seven stripes during the blastoderm stage, and each stripe overlaps with the even-skipped stripes. tenm mutants show a phenotype resembling that of odd-paired (opa), a member of the pair-rule class of segmentation genes. Thus, Tenm is the first example of a pair-rule gene product acting from outside the cell. While the Tenm protein is under the control of fushi tarazu and even-skipped, but not of opa, at least two pair-rule genes, paired (prd) and sloppy paired (slp), and all segment-polarity genes analysed to date are under the control of tenm. Our data suggest that Tenm initiates a signal transduction cascade which acts, via or in concert with opa, on downstream targets such as prd, slp, gooseberry, engrailed and wingless, leading to an opa-like phenotype. Images PMID:8070401

  6. DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

    PubMed Central

    Aziz, Azhari; Harrop, Sean P.; Bishop, Naomi E.

    2011-01-01

    Background Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation. PMID:21264219

  7. Chromosome-wide analysis of gene function by RNA interference in the african trypanosome.

    PubMed

    Subramaniam, Chandra; Veazey, Paul; Redmond, Seth; Hayes-Sinclair, Jamie; Chambers, Emma; Carrington, Mark; Gull, Keith; Matthews, Keith; Horn, David; Field, Mark C

    2006-09-01

    Trypanosomatids of the order Kinetoplastida are major contributors to global disease and morbidity, and understanding their basic biology coupled with the development of new drug targets represents a critical need. Additionally, trypanosomes are among the more accessible divergent eukaryote experimental systems. The genome of Trypanosoma brucei contains 8,131 predicted open reading frames (ORFs), of which over half have no known homologues beyond the Kinetoplastida and a substantial number of others are poorly defined by in silico analysis. Thus, a major challenge following completion of the T. brucei genome sequence is to obtain functional data for all trypanosome ORFs. As T. brucei is more experimentally tractable than the related Trypanosoma cruzi and Leishmania spp. and shares >75% of their genes, functional analysis of T. brucei has the potential to inform a range of parasite biology. Here, we report methods for systematic mRNA ablation by RNA interference (RNAi) and for phenotypic analysis, together with online data dissemination. This represents the first systematic analysis of gene function in a parasitic organism. In total, 210 genes have been targeted in the bloodstream form parasite, representing an essentially complete phenotypic catalogue of chromosome I together with a validation set. Over 30% of the chromosome I genes generated a phenotype when targeted by RNAi; most commonly, this affected cell growth, viability, and/or cell cycle progression. RNAi against approximately 12% of ORFs was lethal, and an additional 11% had growth defects but retained short-term viability in culture. Although we found no evidence for clustering or a bias towards widely evolutionarily conserved genes within the essential ORF cohort, the putative chromosome I centromere is adjacent to a domain containing genes with no associated phenotype. Involvement of such a large proportion of genes in robust growth in vitro indicates that a high proportion of the expressed trypanosome genome is required for efficient propagation; many of these gene products represent potential drug targets. PMID:16963636

  8. Genome-Wide Distribution, Organisation and Functional Characterization of Disease Resistance and Defence Response Genes across Rice Species

    PubMed Central

    Singh, Sangeeta; Chand, Suresh; Singh, N. K.; Sharma, Tilak Raj

    2015-01-01

    The resistance (R) genes and defense response (DR) genes have become very important resources for the development of disease resistant cultivars. In the present investigation, genome-wide identification, expression, phylogenetic and synteny analysis was done for R and DR-genes across three species of rice viz: Oryza sativa ssp indica cv 93-11, Oryza sativa ssp japonica and wild rice species, Oryza brachyantha. We used the in silico approach to identify and map 786 R -genes and 167 DR-genes, 672 R-genes and 142 DR-genes, 251 R-genes and 86 DR-genes in the japonica, indica and O. brachyanth a genomes, respectively. Our analysis showed that 60.5% and 55.6% of the R-genes are tandemly repeated within clusters and distributed over all the rice chromosomes in indica and japonica genomes, respectively. The phylogenetic analysis along with motif distribution shows high degree of conservation of R- and DR-genes in clusters. In silico expression analysis of R-genes and DR-genes showed more than 85% were expressed genes showing corresponding EST matches in the databases. This study gave special emphasis on mechanisms of gene evolution and duplication for R and DR genes across species. Analysis of paralogs across rice species indicated 17% and 4.38% R-genes, 29% and 11.63% DR-genes duplication in indica and Oryza brachyantha, as compared to 20% and 26% duplication of R-genes and DR-genes in japonica respectively. We found that during the course of duplication only 9.5% of R- and DR-genes changed their function and rest of the genes have maintained their identity. Syntenic relationship across three genomes inferred that more orthology is shared between indica and japonica genomes as compared to brachyantha genome. Genome wide identification of R-genes and DR-genes in the rice genome will help in allele mining and functional validation of these genes, and to understand molecular mechanism of disease resistance and their evolution in rice and related species. PMID:25902056

  9. A highly conserved gene island of three genes on chromosome 3B of hexaploid wheat: diverse gene function and genomic structure maintained in a tightly linked block

    PubMed Central

    2010-01-01

    Background The complexity of the wheat genome has resulted from waves of retrotransposable element insertions. Gene deletions and disruptions generated by the fast replacement of repetitive elements in wheat have resulted in disruption of colinearity at a micro (sub-megabase) level among the cereals. In view of genomic changes that are possible within a given time span, conservation of genes between species tends to imply an important functional or regional constraint that does not permit a change in genomic structure. The ctg1034 contig completed in this paper was initially studied because it was assigned to the Sr2 resistance locus region, but detailed mapping studies subsequently assigned it to the long arm of 3B and revealed its unusual features. Results BAC shotgun sequencing of the hexaploid wheat (Triticum aestivum cv. Chinese Spring) genome has been used to assemble a group of 15 wheat BACs from the chromosome 3B physical map FPC contig ctg1034 into a 783,553 bp genomic sequence. This ctg1034 sequence was annotated for biological features such as genes and transposable elements. A three-gene island was identified among >80% repetitive DNA sequence. Using bioinformatics analysis there were no observable similarity in their gene functions. The ctg1034 gene island also displayed complete conservation of gene order and orientation with syntenic gene islands found in publicly available genome sequences of Brachypodium distachyon, Oryza sativa, Sorghum bicolor and Zea mays, even though the intergenic space and introns were divergent. Conclusion We propose that ctg1034 is located within the heterochromatic C-band region of deletion bin 3BL7 based on the identification of heterochromatic tandem repeats and presence of significant matches to chromodomain-containing gypsy LTR retrotransposable elements. We also speculate that this location, among other highly repetitive sequences, may account for the relative stability in gene order and orientation within the gene island. Sequence data from this article have been deposited with the GenBank Data Libraries under accession no. GQ422824 PMID:20507561

  10. A Multifunctional Mutagenesis System for Analysis of Gene Function in Zebrafish

    PubMed Central

    Quach, Helen Ngoc Bao; Tao, Shijie; Vrljicak, Pavle; Joshi, Adita; Ruan, Hua; Sukumaran, Rashmi; Varshney, Gaurav K.; LaFave, Matthew C.; Burgess, Shawn M.; Winkler, Christoph; Emelyanov, Alexander; Parinov, Sergey; Sampath, Karuna

    2015-01-01

    Since the sequencing of the human reference genome, many human disease-related genes have been discovered. However, understanding the functions of all the genes in the genome remains a challenge. The biological activities of these genes are usually investigated in model organisms such as mice and zebrafish. Large-scale mutagenesis screens to generate disruptive mutations are useful for identifying and understanding the activities of genes. Here, we report a multifunctional mutagenesis system in zebrafish using the maize Ds transposon. Integration of the Ds transposable element containing an mCherry reporter for protein trap events and an EGFP reporter for enhancer trap events produced a collection of transgenic lines marking distinct cell and tissue types, and mutagenized genes in the zebrafish genome by trapping and prematurely terminating endogenous protein coding sequences. We obtained 642 zebrafish lines with dynamic reporter gene expression. The characterized fish lines with specific expression patterns will be made available through the European Zebrafish Resource Center (EZRC), and a database of reporter expression is available online (http://fishtrap.warwick.ac.uk/). Our approach complements other efforts using zebrafish to facilitate functional genomic studies in this model of human development and disease. PMID:25840430

  11. A Survey of Essential Gene Function in the Yeast Cell Division Cycle

    PubMed Central

    Yu, Lisa; Castillo, Lourdes Peña; Mnaimneh, Sanie

    2006-01-01

    Mutations impacting specific stages of cell growth and division have provided a foundation for dissecting mechanisms that underlie cell cycle progression. We have undertaken an objective examination of the yeast cell cycle through flow cytometric analysis of DNA content in TetO7 promoter mutant strains representing 75% of all essential yeast genes. More than 65% of the strains displayed specific alterations in DNA content, suggesting that reduced function of an essential gene in most cases impairs progression through a specific stage of the cell cycle. Because of the large number of essential genes required for protein biosynthesis, G1 accumulation was the most common phenotype observed in our analysis. In contrast, relatively few mutants displayed S-phase delay, and most of these were defective in genes required for DNA replication or nucleotide metabolism. G2 accumulation appeared to arise from a variety of defects. In addition to providing a global view of the diversity of essential cellular processes that influence cell cycle progression, these data also provided predictions regarding the functions of individual genes: we identified four new genes involved in protein trafficking (NUS1, PHS1, PGA2, PGA3), and we found that CSE1 and SMC4 are important for DNA replication. PMID:16943325

  12. Captured metagenomics: large-scale targeting of genes based on ‘sequence capture’ reveals functional diversity in soils

    PubMed Central

    Manoharan, Lokeshwaran; Kushwaha, Sandeep K.; Hedlund, Katarina; Ahrén, Dag

    2015-01-01

    Microbial enzyme diversity is a key to understand many ecosystem processes. Whole metagenome sequencing (WMG) obtains information on functional genes, but it is costly and inefficient due to large amount of sequencing that is required. In this study, we have applied a captured metagenomics technique for functional genes in soil microorganisms, as an alternative to WMG. Large-scale targeting of functional genes, coding for enzymes related to organic matter degradation, was applied to two agricultural soil communities through captured metagenomics. Captured metagenomics uses custom-designed, hybridization-based oligonucleotide probes that enrich functional genes of interest in metagenomic libraries where only probe-bound DNA fragments are sequenced. The captured metagenomes were highly enriched with targeted genes while maintaining their target diversity and their taxonomic distribution correlated well with the traditional ribosomal sequencing. The captured metagenomes were highly enriched with genes related to organic matter degradation; at least five times more than similar, publicly available soil WMG projects. This target enrichment technique also preserves the functional representation of the soils, thereby facilitating comparative metagenomics projects. Here, we present the first study that applies the captured metagenomics approach in large scale, and this novel method allows deep investigations of central ecosystem processes by studying functional gene abundances. PMID:26490729

  13. Captured metagenomics: large-scale targeting of genes based on 'sequence capture' reveals functional diversity in soils.

    PubMed

    Manoharan, Lokeshwaran; Kushwaha, Sandeep K; Hedlund, Katarina; Ahrén, Dag

    2015-12-01

    Microbial enzyme diversity is a key to understand many ecosystem processes. Whole metagenome sequencing (WMG) obtains information on functional genes, but it is costly and inefficient due to large amount of sequencing that is required. In this study, we have applied a captured metagenomics technique for functional genes in soil microorganisms, as an alternative to WMG. Large-scale targeting of functional genes, coding for enzymes related to organic matter degradation, was applied to two agricultural soil communities through captured metagenomics. Captured metagenomics uses custom-designed, hybridization-based oligonucleotide probes that enrich functional genes of interest in metagenomic libraries where only probe-bound DNA fragments are sequenced. The captured metagenomes were highly enriched with targeted genes while maintaining their target diversity and their taxonomic distribution correlated well with the traditional ribosomal sequencing. The captured metagenomes were highly enriched with genes related to organic matter degradation; at least five times more than similar, publicly available soil WMG projects. This target enrichment technique also preserves the functional representation of the soils, thereby facilitating comparative metagenomics projects. Here, we present the first study that applies the captured metagenomics approach in large scale, and this novel method allows deep investigations of central ecosystem processes by studying functional gene abundances. PMID:26490729

  14. Functional Analysis of Sirtuin Genes in Multiple Plasmodium falciparum Strains

    PubMed Central

    Merrick, Catherine J.; Jiang, Rays H. Y.; Skillman, Kristen M.; Samarakoon, Upeka; Moore, Rachel M.; Dzikowski, Ron; Ferdig, Michael T.; Duraisingh, Manoj T.

    2015-01-01

    Plasmodium falciparum, the causative agent of severe human malaria, employs antigenic variation to avoid host immunity. Antigenic variation is achieved by transcriptional switching amongst polymorphic var genes, enforced by epigenetic modification of chromatin. The histone-modifying ‘sirtuin’ enzymes PfSir2a and PfSir2b have been implicated in this process. Disparate patterns of var expression have been reported in patient isolates as well as in cultured strains. We examined var expression in three commonly used laboratory strains (3D7, NF54 and FCR-3) in parallel. NF54 parasites express significantly lower levels of var genes compared to 3D7, despite the fact that 3D7 was originally a clone of the NF54 strain. To investigate whether this was linked to the expression of sirtuins, genetic disruption of both sirtuins was attempted in all three strains. No dramatic changes in var gene expression occurred in NF54 or FCR-3 following PfSir2b disruption, contrasting with previous observations in 3D7. In 3D7, complementation of the PfSir2a genetic disruption resulted in a significant decrease in previously-elevated var gene expression levels, but with the continued expression of multiple var genes. Finally, rearranged chromosomes were observed in the 3D7 PfSir2a knockout line. Our results focus on the potential for parasite genetic background to contribute to sirtuin function in regulating virulence gene expression and suggest a potential role for sirtuins in maintaining genome integrity. PMID:25780929

  15. Muscle architecture in relation to function.

    PubMed

    Gans, C; Gaunt, A S

    1991-01-01

    Animal muscles generate forces and induce movements at desirable rates. These roles are interactive and must be considered together. Performance of the organism and survival of the species also involve potential optimization of control and of energy consumption. Further, individual variability arising partly via ontogeny and partly from phylogenetic history often has pronounced and sometime conflicting effects on structures and their uses. Hence, animal bodies are generally adequate for their tasks rather than being elegantly matched to them. For muscle, matching to role is reflected at all levels of muscular organization, from the nature of the sarcoplasm and contractile filaments to architectural arrangements of the parts and whole of organs. Vertebrate muscles are often analyzed by mapping their placement and then "explaining" this on the basis of currently observed roles. A recent alternative asks the obverse; given a mass of tissue that may be developed and maintained at a particular cost, what predictions do physical principles permit about its placement. Three architectural patterns that deserve discussion are the classical arrangement of fibers in pinnate patterns, the more recent assumption of sarcomere equivalence, and the issue of compartmentation. All have potential functional implications. 1. The assumption of equivalence of the sarcomeres of motor units allows predictions of the fiber length between sites of origin and insertion. In musculoskeletal systems that induce rotation, the observed (but not the pinnation-associated) insertion angle will differ with the radial lines on which the fibers insert. In a dynamic contraction inducing rotation, a shift of moment arm has no effect for muscles of equal mass. 2. Classical pinnate muscles contain many relatively short fibers positioned in parallel but at an angle to the whole muscle, reducing the per fiber force contribution. However, the total physiological cross-section and total muscle force are thus increased relative to arrangements with fibers parallel to the whole muscle. Equivalent muscles may be placed in various volumetric configurations matching other demands of the organism. The loss of fiber force due to (pinnate, not equivalent) angulation is compensated for by the reduced shortening of fibers in multipinnate arrays. 3. Compartmentation, i.e., the subdivision of muscles into independently controlled, spatially discrete volumes, is likely ubiquitous. Differential activation of the columns of radial arrays may facilitate change of vector and with this of function. Compartmentation is apt to be particularly important in strap muscles with short fiber architecture; their motor units generally occupy columnar, rather than transversely stacked, subdivisions; this may affect recovery from fiber atrophy and degeneration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1791182

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

    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

  18. Cloning and functional characterization of carotenoid cleavage dioxygenase 4 genes.

    PubMed

    Huang, Fong-Chin; Molnár, Péter; Schwab, Wilfried

    2009-01-01

    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 x domestica, MdCCD4), chrysanthemum (Chrysanthemum x morifolium, CmCCD4a), rose (Rosa x 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 beta-carotene well to yield beta-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-zeta-carotene and lycopene. In vitro assays, however, demonstrated the breakdown of 8'-apo-beta-caroten-8'-al by AtCCD4 and RdCCD4 to beta-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

  19. Cloning and functional characterization of carotenoid cleavage dioxygenase 4 genes

    PubMed Central

    Huang, Fong-Chin; Molnár, Péter; Schwab, Wilfried

    2009-01-01

    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

  20. Identification of Genes Related to Growth and Lipid Deposition from Transcriptome Profiles of Pig Muscle Tissue

    PubMed Central

    Chamba, Yangzom; Zhang, Bo; Shang, Peng; Zhang, Hao; Wu, Changxin

    2015-01-01

    Transcriptome profiles established using high-throughput sequencing can be effectively used for screening genome-wide differentially expressed genes (DEGs). RNA sequences (from RNA-seq) and microRNA sequences (from miRNA-seq) from the tissues of longissimus dorsi muscle of two indigenous Chinese pig breeds (Diannan Small-ear pig [DSP] and Tibetan pig [TP]) and two introduced pig breeds (Landrace [LL] and Yorkshire [YY]) were examined using HiSeq 2000 to identify and compare the differential expression of functional genes related to muscle growth and lipid deposition. We obtained 27.18 G clean data through the RNA-seq and detected that 18,208 genes were positively expressed and 14,633 of them were co-expressed in the muscle tissues of the four samples. In all, 315 DEGs were found between the Chinese pig group and the introduced pig group, 240 of which were enriched with functional annotations from the David database and significantly enriched in 27 Gene Ontology (GO) terms that were mainly associated with muscle fiber contraction, cadmium ion binding, response to organic substance and contractile fiber part. Based on functional annotation, we identified 85 DEGs related to growth traits that were mainly involved in muscle tissue development, muscle system process, regulation of cell development, and growth factor binding, and 27 DEGs related to lipid deposition that were mainly involved in lipid metabolic process and fatty acid biosynthetic process. With miRNA-seq, we obtained 23.78 M reads and 320 positively expressed miRNAs from muscle tissues, including 271 known pig miRNAs and 49 novel miRNAs. In those 271 known miRNAs, 20 were higher and 10 lower expressed in DSP-TP than in LL-YY. The target genes of the 30 miRNAs were mainly participated in MAPK, GnRH, insulin and Calcium signaling pathway and others involved cell development, growth and proliferation, etc. Combining the DEGs and the differentially expressed (DE) miRNAs, we drafted a network of 46 genes and 18 miRNAs for regulating muscle growth and a network of 15 genes and 16 miRNAs for regulating lipid deposition. We identified that CAV2, MYOZ2, FRZB, miR-29b, miR-122, miR-145-5p and miR-let-7c, etc, were key genes or miRNAs regulating muscle growth, and FASN, SCD, ADORA1, miR-4332, miR-182, miR-92b-3p, miR-let-7a and miR-let-7e, etc, were key genes or miRNAs regulating lipid deposition. The quantitative expressions of eight DEGs and seven DE miRNAs measured with real-time PCR certified that the results of differential expression genes or miRNAs were reliable. Thus, 18,208 genes and 320 miRNAs were positively expressed in porcine longissimus dorsi muscle. We obtained 85 genes and 18 miRNAs related to muscle growth and 27 genes and 16 miRNAs related to lipid deposition, which provided new insights into molecular mechanism of the economical traits in pig. PMID:26505482

  1. Identification of potential COPD genes based on multi-omics data at the functional level.

    PubMed

    Liu, Zhe; Li, Wan; Lv, Junjie; Xie, Ruiqiang; Huang, Hao; Li, Yiran; He, Yuehan; Jiang, Jing; Chen, Binbin; Guo, Shanshan; Chen, Lina

    2016-01-15

    Chronic obstructive pulmonary disease (COPD) is a complex disease, which involves dysfunctions in multi-omics. The changes in biological processes, such as adhesion junction, signaling transduction, transcriptional regulation, and cell proliferation, will lead to the occurrence of COPD. A novel systematic approach MMMG (Methylation-MicroRNA-MRNA-GO) was proposed to identify potential COPD genes by integrating function information with a methylation profile, a microRNA expression profile and an mRNA expression profile. 8 co-functional classes and 102 potential COPD genes were identified. These genes displayed a high performance in classifying COPD patients and normal samples, revealed COPD-related pathways, and have been confirmed to be associated with COPD by Matthews correlation coefficient (MCC)-values, literature, an independent data set, and pathways. The MMMG method that analyzed multi-omics data at the functional level could effectively identify potential COPD genes. These potential COPD genes would provide in-depth insights into understanding the complexity of COPD genome landscapes, improve the early diagnostics, and guide new efforts to develop therapeutics in the future. PMID:26575263

  2. Enantioselective Degradation Mechanism of Beta-Cypermethrin in Soil From the Perspective of Functional Genes.

    PubMed

    Yang, Zhong-Hua; Ji, Guo-Dong

    2015-12-01

    The behavior and mechanisms of the enantioselective degradation of beta-cypermethrin were studied in soil. The four isomers were degraded at different rates, and the enantiomer fractions of alpha-cypermethrin and theta-cypermethrin exceeded 0.5. Moreover, 3-phenoxybenzoic acid, phenol, and protocatechuic acid were detected; based on the presence of these metabolites, we predicted the degradation pathway and identified the functional genes that are related to this degradation process. We established quantitative relationships between the data on degradation kinetics and functional genes; we found that the quantitative relationships between different enantiomers differed even under the same conditions, and the genes pobA and pytH played key roles in limiting the degradation rate. Data obtained using path analysis revealed that the same gene had different direct and indirect effects on the degradation of different isomers. A mechanism was successfully proposed to explain the selective degradation of chiral compounds based on the perspective of functional genes. Chirality 27:929-935, 2015. © 2015 Wiley Periodicals, Inc. PMID:26403376

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

    PubMed Central

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

    2014-01-01

    Resistance against diseases affects profitability of rainbow trout. Limited information is available about functions and mechanisms of teleost immune pathways. Immunogenomics provides powerful tools to determine disease resistance genes/gene pathways and develop genetic markers for genomic selection. RNA-Seq sequencing of the rainbow trout spleen yielded 93,532,200 reads (100 bp). High quality reads were assembled into 43,047 contigs. 26,333 (61.17%) of the contigs had hits to the NR protein database and 7024 (16.32%) had hits to the KEGG database. Gene ontology showed significant percentages of transcripts assigned to binding (51%), signaling (7%), response to stimuli (9%) and receptor activity (4%) suggesting existence of many immune-related genes. KEGG annotation revealed 2825 sequences belonging to “organismal systems” with the highest number of sequences, 842 (29.81%), assigned to immune system. A number of sequences were identified for the first time in rainbow trout belonging to Toll-like receptor signaling (35), B cell receptor signaling pathway (44), T cell receptor signaling pathway (56), chemokine signaling pathway (73), Fc gamma R-mediated phagocytosis (52), leukocyte transendothelial migration (60) and NK cell mediated cytotoxicity (42). In addition, 51 transcripts were identified as spleen-specific genes. The list includes 277 full-length cDNAs. The presence of a large number of immune-related genes and pathways similar to other vertebrates suggests that innate and adaptive immunity in fish are conserved. This study provides deep-sequence data of rainbow trout spleen transcriptome and identifies many new immune-related genes and full-length cDNAs. This data will help identify allelic variations suitable for genomic selection and genetic manipulation in aquaculture. PMID:25352861

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

    PubMed

    Kurbidaeva, Amina; Ezhova, Tatiana; Novokreshchenova, Maria

    2014-12-01

    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

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Technical Reports Server (NTRS)

    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

    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.

  7. Sugarcane Functional Genomics: Gene Discovery for Agronomic Trait Development

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

    2013-01-01

    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

  9. Functions of BET proteins in erythroid gene expression.

    PubMed

    Stonestrom, Aaron J; Hsu, Sarah C; Jahn, Kristen S; Huang, Peng; Keller, Cheryl A; Giardine, Belinda M; Kadauke, Stephan; Campbell, Amy E; Evans, Perry; Hardison, Ross C; Blobel, Gerd A

    2015-04-30

    Inhibitors of bromodomain and extraterminal motif proteins (BETs) are being evaluated for the treatment of cancer and other diseases, yet much remains to be learned about how BET proteins function during normal physiology. We used genomic and genetic approaches to examine BET function in a hematopoietic maturation system driven by GATA1, an acetylated transcription factor previously shown to interact with BETs. We found that BRD2, BRD3, and BRD4 were variably recruited to GATA1-regulated genes, with BRD3 binding the greatest number of GATA1-occupied sites. Pharmacologic BET inhibition impaired GATA1-mediated transcriptional activation, but not repression, genome-wide. Mechanistically, BETs promoted chromatin occupancy of GATA1 and subsequently supported transcriptional activation. Using a combination of CRISPR-Cas9-mediated genomic engineering and shRNA approaches, we observed that depletion of either BRD2 or BRD4 alone blunted erythroid gene activation. Surprisingly, depletion of BRD3 only affected erythroid transcription in the context of BRD2 deficiency. Consistent with functional overlap among BET proteins, forced BRD3 expression substantially rescued defects caused by BRD2 deficiency. These results suggest that pharmacologic BET inhibition should be interpreted in the context of distinct steps in transcriptional activation and overlapping functions among BET family members. PMID:25696920

  10. Immunity-related genes in Ixodes scapularis—perspectives from genome information

    PubMed Central

    Smith, Alexis A.; Pal, Utpal

    2014-01-01

    Ixodes scapularis, commonly known as the deer tick, transmits a wide array of human and animal pathogens including Borrelia burgdorferi. Despite substantial advances in our understanding of immunity in model arthropods, including other disease vectors, precisely how I. scapularis immunity functions and influences persistence of invading pathogens remains largely unknown. This review provides a comprehensive analysis of the recently sequenced I. scapularis genome for the occurrence of immune-related genes and related pathways. We will also discuss the potential influence of immunity-related genes on the persistence of tick-borne pathogens with an emphasis on the Lyme disease pathogen B. burgdorferi. Further enhancement of our knowledge of tick immune responses is critical to understanding the molecular basis of the persistence of tick-borne pathogens and development of novel interventions against the relevant infections. PMID:25202684

  11. p53 genes function to restrain mobile elements.

    PubMed

    Wylie, Annika; Jones, Amanda E; D'Brot, Alejandro; Lu, Wan-Jin; Kurtz, Paula; Moran, John V; Rakheja, Dinesh; Chen, Kenneth S; Hammer, Robert E; Comerford, Sarah A; Amatruda, James F; Abrams, John M

    2016-01-01

    Throughout the animal kingdom, p53 genes govern stress response networks by specifying adaptive transcriptional responses. The human member of this gene family is mutated in most cancers, but precisely how p53 functions to mediate tumor suppression is not well understood. Using Drosophila and zebrafish models, we show that p53 restricts retrotransposon activity and genetically interacts with components of the piRNA (piwi-interacting RNA) pathway. Furthermore, transposon eruptions occurring in the p53(-) germline were incited by meiotic recombination, and transcripts produced from these mobile elements accumulated in the germ plasm. In gene complementation studies, normal human p53 alleles suppressed transposons, but mutant p53 alleles from cancer patients could not. Consistent with these observations, we also found patterns of unrestrained retrotransposons in p53-driven mouse and human cancers. Furthermore, p53 status correlated with repressive chromatin marks in the 5' sequence of a synthetic LINE-1 element. Together, these observations indicate that ancestral functions of p53 operate through conserved mechanisms to contain retrotransposons. Since human p53 mutants are disabled for this activity, our findings raise the possibility that p53 mitigates oncogenic disease in part by restricting transposon mobility. PMID:26701264

  12. Identifying genes related to choriogenesis in insect panoistic ovaries by Suppression Subtractive Hybridization

    PubMed Central

    Irles, Paula; Bellés, Xavier; Piulachs, M Dolors

    2009-01-01

    Background Insect ovarioles are classified into two categories: panoistic and meroistic, the later having apparently evolved from an ancestral panoistic type. Molecular data on oogenesis is practically restricted to meroistic ovaries. If we aim at studying the evolutionary transition from panoistic to meroistic, data on panoistic ovaries should be gathered. To this end, we planned the construction of a Suppression Subtractive Hybridization (SSH) library to identify genes involved in panoistic choriogenesis, using the cockroach Blattella germanica as model. Results We constructed a post-vitellogenic ovary library by SSH to isolate genes involved in choriogenesis in B. germanica. The tester library was prepared with an ovary pool from 6- to 7-day-old females, whereas the driver library was prepared with an ovary pool from 3- to 4-day-old females. From the SSH library, we obtained 258 high quality sequences which clustered into 34 unique sequences grouped in 19 contigs and 15 singlets. The sequences were compared against non-redundant NCBI databases using BLAST. We found that 44% of the unique sequences had homologous sequences in known genes of other organisms, whereas 56% had no significant similarity to any of the databases entries. A Gene Ontology analysis was carried out, classifying the 34 sequences into different functional categories. Seven of these gene sequences, representative of different categories and processes, were chosen to perform expression studies during the first gonadotrophic cycle by real-time PCR. Results showed that they were mainly expressed during post-vitellogenesis, which validates the SSH technique. In two of them corresponding to novel genes, we demonstrated that they are specifically expressed in the cytoplasm of follicular cells in basal oocytes at the time of choriogenesis. Conclusion The SSH approach has proven to be useful in identifying ovarian genes expressed after vitellogenesis in B. germanica. For most of the genes, functions related to choriogenesis are postulated. The relatively high percentage of novel genes obtained and the practical absence of chorion genes typical of meroistic ovaries suggest that mechanisms regulating chorion formation in panoistic ovaries are significantly different from those of meroistic ones. PMID:19405973

  13. Afforestation Alters the Composition of Functional Genes in Soil and Biogeochemical Processes

    E-print Network

    Post, Wilfred M.

    , however their belowground carbon cycle changes have not been fully investigated. · Functional genes with changes in soil biogeochemistry, in part through altered abundance of overall functional gene types ratherAfforestation Alters the Composition of Functional Genes in Soil and Biogeochemical Processes

  14. Comparison and Evaluation of Statistical-Learning Methods for Gene Function Prediction in Arabidopsis

    E-print Network

    Bonner, Anthony

    Comparison and Evaluation of Statistical-Learning Methods for Gene Function Prediction Lan #12;Abstract Comparison and Evaluation of Statistical-Learning Methods for Gene Function responses to stresses. We evaluated and compared five basic statis- tical learning methods for gene function

  15. Robustness in Gene Circuits: Clustering of Functional Responses Mary J. Dunlop and Michael E. Wall

    E-print Network

    Dunlop, Mary

    Robustness in Gene Circuits: Clustering of Functional Responses Mary J. Dunlop and Michael E. Wall to satisfy prescribed function requirements, in biology it is often necessary to infer gene-circuit function from incomplete data on gene-circuit structure. By using the feed-forward loop as a model system

  16. Breast and Prostate Cancer and Hormone-Related Gene Variant Study

    Cancer.gov

    The Breast and Prostate Cancer and Hormone-Related Gene Variant Study allows large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism.

  17. Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

    PubMed Central

    Takahara, Yoshiyuki; Takahashi, Mitsuo; Zhang, Qing-Wei; Wagatsuma, Hirotaka; Mori, Maiko; Tamori, Akihiro; Shiomi, Susumu; Nishiguchi, Shuhei

    2008-01-01

    AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis. PMID:18395900

  18. Transcriptome profiling analysis of naked carp (Gymnocypris przewalskii) provides insights into the immune-related genes in highland fish.

    PubMed

    Tong, Chao; Zhang, Cunfang; Zhang, Renyi; Zhao, Kai

    2015-10-01

    The naked carp, Gymnocypris przewalskii, is one of the dominant aquaculture fish species in Qinghai Province, China. Its wild stocks have severely suffered from overfishing, and the farming species are vulnerable to various pathogens infections. Here we report the first immune-related tissues transcriptome of a wild naked carp using a deep sequencing approach. A total of 158,087 unigenes are generated, 2687 gill-specific gene and 3215 kidney-specific genes are identified, respectively. Gene ontology analysis shows that 51,671 unigenes are involved in three major functional categories: biological process, cellular component, and molecular function. Further analysis shows that numerous consensus sequences are homologous to known immune-related genes. Pathways mapping annotate 56,270 unigenes and identify a large number of immune-related pathways. In addition, we focus on the immune-related genes and gene family in Toll-like receptor signaling pathway involved in innate immunity, including toll-like receptors (TLRs), interferon regulatory factors (IRFs), interleukins (ILs) and tumor necrosis factors (TNFs). Eventually, we identify 5 TLRs, 4 IRFs, 3 ILs and 2 TNFs with a completed coding sequence though mining the transcriptome data. Phylogeny analysis shows these genes of naked carp are mostly close to zebrafish. Protein domain and selection pressure analyses together show that all these genes are highly conserved in gene sequence and protein domain structure with other species, and purifying selection underwent in these genes, implied functionally important features are conserved in the genes above. Intriguingly, we detect positive selection signals in naked carp TLR4, and significant divergence occurred among tested species TLR4, suggested that naked carp TLR4 function may be affected. Finally, we identify 23,867 simple sequence repeat (SSR) marks in this transcriptome. Taken together, this study not only contributes a large number of candidate genes in naked carp immunity, and also helps improve current understanding of immunogenetics basis and evolutionary history of immune related genes and gene family in highland fish species. PMID:26117731

  19. Non-target effects of repeated chlorothalonil application on soil nitrogen cycling: The key functional gene study.

    PubMed

    Zhang, Manyun; Xu, Zhihong; Teng, Ying; Christie, Peter; Wang, Jun; Ren, Wenjie; Luo, Yongming; Li, Zhengao

    2016-02-01

    The widespread and increasing application of chlorothalonil (CTN) raises concerns about its non-target impacts, but little information is available on the effect of CTN on the key functional genes related to soil nitrogen (N) cycling, especially in the case of repeated applications. In the present study, a microcosm incubation was conducted to determine CTN residues and the impacts on the abundances of key functional genes related to N cycling after repeated CTN applications. The results demonstrated that repeated CTN applications at the recommended application rate and five times the recommended rate led to the accumulation of CTN residue in soil at concentrations of 5.59 and 78.79mgkg(-1), respectively, by the end of incubation. Real time PCR (RT-PCR) revealed that repeated CTN applications had negative effects on the chiA and aprA gene abundances. There were significantly negative correlations between CTN residues and abundances of AOA and AOB genes. In addition, the abundances of key functional genes involved in soil denitrification were declined by repeated CTN applications with the sole exception of the nosZ gene. This study suggests that repeated CTN applications could lead to the accumulation of CTN residue and generate somewhat inconsistent and erratic effects on the abundances of key functional genes related to soil N cycling. PMID:26613517

  20. Relative partition function of Coulomb plus delta interaction

    E-print Network

    Sergio Albeverio; Claudio Cacciapuoti; Mauro Spreafico

    2015-10-16

    The relative partition function and the relative zeta function of the perturbation of the Laplace operator by a Coulomb potential plus a point interaction centered in the origin is discussed. Applications to the study of the Casimir effect are indicated.

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

    PubMed Central

    Tsai, Chia-Hong; Bullard, Blair; Cornish, Adam J.; Harvey, Christopher; Reca, Ida-Barbara; Thornburg, Chelsea; Achawanantakun, Rujira; Buehl, Christopher J.; Campbell, Michael S.; Cavalier, David; Childs, Kevin L.; Clark, Teresa J.; Deshpande, Rahul; Erickson, Erika; Armenia Ferguson, Ann; Handee, Witawas; Kong, Que; Li, Xiaobo; Liu, Bensheng; Lundback, Steven; Peng, Cheng; Roston, Rebecca L.; Sanjaya; Simpson, Jeffrey P.; TerBush, Allan; Warakanont, Jaruswan; Zäuner, Simone; Farre, Eva M.; Hegg, Eric L.; Jiang, Ning; Kuo, Min-Hao; Lu, Yan; Niyogi, Krishna K.; Ohlrogge, John; Osteryoung, Katherine W.; Shachar-Hill, Yair; Sears, Barbara B.; Sun, Yanni; Takahashi, Hideki; Yandell, Mark; Shiu, Shin-Han; Benning, Christoph

    2012-01-01

    Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks, although no single species has emerged as a preferred organism. Moreover, adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candidate species. Heterokonts of the genus Nannochloropsis naturally have high cellular oil content and are already in use for industrial production of high-value lipid products. First success in applying reverse genetics by targeted gene replacement makes Nannochloropsis oceanica an attractive model to investigate the cell and molecular biology and biochemistry of this fascinating organism group. Here we present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA sequencing data from nitrogen-replete and nitrogen-depleted growth conditions support a total of 11,973 genes, of which in addition to automatic annotation some were manually inspected to predict the biochemical repertoire for this organism. Among others, more than 100 genes putatively related to lipid metabolism, 114 predicted transcription factors, and 109 transcriptional regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire with the recently published N. gaditana genome identified 2,649 genes likely specific to N. oceanica CCMP1779. Many of these N. oceanica–specific genes have putative orthologs in other species or are supported by transcriptional evidence. However, because similarity-based annotations are limited, functions of most of these species-specific genes remain unknown. Aside from the genome sequence and its analysis, protocols for the transformation of N. oceanica CCMP1779 are provided. The availability of genomic and transcriptomic data for Nannochloropsis oceanica CCMP1779, along with efficient transformation protocols, provides a blueprint for future detailed gene functional analysis and genetic engineering of Nannochloropsis species by a growing academic community focused on this genus. PMID:23166516

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

    PubMed Central

    Masseroli, Marco; Bellistri, Elisa; Franceschini, Andrea; Pinciroli, Francesco

    2007-01-01

    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 analysis and mining. Results Exploiting protein information in Pfam and InterPro databanks, we developed and added in GFINDer original modules specifically devoted to the exploration and analysis of functional signatures of gene protein products. They allow annotating numerous user-classified nucleotide sequence identifiers with controlled information on related protein families, domains and functional sites, classifying them according to such protein annotation categories, and statistically analyzing the obtained classifications. In particular, when uploaded nucleotide sequence identifiers are subdivided in classes, the Statistics Protein Families&Domains module allows estimating relevance of Pfam or InterPro controlled annotations for the uploaded genes by highlighting protein signatures significantly more represented within user-defined classes of genes. In addition, the Logistic Regression module allows identifying protein functional signatures that better explain the considered gene classification. Conclusion Novel GFINDer modules provide genomic protein family and domain analyses supporting better functional interpretation of gene classes, for instance defined through statistical and clustering analyses of gene expression results from microarray experiments. They can hence help understanding fundamental biological processes and complex cellular mechanisms influenced by protein domain composition, and contribute to unveil new biomedical knowledge about the codifying genes. PMID:17430558

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

    PubMed Central

    2012-01-01

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

  4. Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo

    PubMed Central

    Cui, Miao; Siriwon, Natnaree; Li, Enhu; Davidson, Eric H.; Peter, Isabelle S.

    2014-01-01

    Wnt signaling affects cell-fate specification processes throughout embryonic development. Here we take advantage of the well-studied gene regulatory networks (GRNs) that control pregastrular sea urchin embryogenesis to reveal the gene regulatory functions of the entire Wnt-signaling system. Five wnt genes, three frizzled genes, two secreted frizzled-related protein 1 genes, and two Dickkopf genes are expressed in dynamic spatial patterns in the pregastrular embryo of Strongylocentrotus purpuratus. We present a comprehensive analysis of these genes in each embryonic domain. Total functions of the Wnt-signaling system in regulatory gene expression throughout the embryo were studied by use of the Porcupine inhibitor C59, which interferes with zygotic Wnt ligand secretion. Morpholino-mediated knockdown of each expressed Wnt ligand demonstrated that individual Wnt ligands are functionally distinct, despite their partially overlapping spatial expression. They target specific embryonic domains and affect particular regulatory genes. The sum of the effects of blocking expression of individual wnt genes is shown to equal C59 effects. Remarkably, zygotic Wnt-signaling inputs are required for only three general aspects of embryonic specification: the broad activation of endodermal GRNs, the regional specification of the immediately adjacent stripe of ectoderm, and the restriction of the apical neurogenic domain. All Wnt signaling in this pregastrular embryo is short range (and/or autocrine). Furthermore, we show that the transcriptional drivers of wnt genes execute important specification functions in the embryonic domains targeted by the ligands, thus connecting the expression and function of wnt genes by encoded cross-regulatory interactions within the specific regional GRNs. PMID:25385617

  5. Gene-Set Local Hierarchical Clustering (GSLHC)—A Gene Set-Based Approach for Characterizing Bioactive Compounds in Terms of Biological Functional Groups

    PubMed Central

    Hsu, Tzu-Ting; Hsu, Chueh-Lin; Liu, Hsueh-Chuan; Lee, Hoong-Chien

    2015-01-01

    Gene-set-based analysis (GSA), which uses the relative importance of functional gene-sets, or molecular signatures, as units for analysis of genome-wide gene expression data, has exhibited major advantages with respect to greater accuracy, robustness, and biological relevance, over individual gene analysis (IGA), which uses log-ratios of individual genes for analysis. Yet IGA remains the dominant mode of analysis of gene expression data. The Connectivity Map (CMap), an extensive database on genomic profiles of effects of drugs and small molecules and widely used for studies related to repurposed drug discovery, has been mostly employed in IGA mode. Here, we constructed a GSA-based version of CMap, Gene-Set Connectivity Map (GSCMap), in which all the genomic profiles in CMap are converted, using gene-sets from the Molecular Signatures Database, to functional profiles. We showed that GSCMap essentially eliminated cell-type dependence, a weakness of CMap in IGA mode, and yielded significantly better performance on sample clustering and drug-target association. As a first application of GSCMap we constructed the platform Gene-Set Local Hierarchical Clustering (GSLHC) for discovering insights on coordinated actions of biological functions and facilitating classification of heterogeneous subtypes on drug-driven responses. GSLHC was shown to tightly clustered drugs of known similar properties. We used GSLHC to identify the therapeutic properties and putative targets of 18 compounds of previously unknown characteristics listed in CMap, eight of which suggest anti-cancer activities. The GSLHC website http://cloudr.ncu.edu.tw/gslhc/ contains 1,857 local hierarchical clusters accessible by querying 555 of the 1,309 drugs and small molecules listed in CMap. We expect GSCMap and GSLHC to be widely useful in providing new insights in the biological effect of bioactive compounds, in drug repurposing, and in function-based classification of complex diseases. PMID:26473729

  6. DEPTH FUNCTIONS AND RELATED FUNCTIONS Depth, Outlyingness, Quantile, and Rank

    E-print Network

    Serfling, Robert

    Outlyingness Functions: Finding "Outliers" in Rd "Outliers" have been under discussion for centuries: Francis Bacon, 1620 ... Daniel Bernoulli, 1777 ... Benjamin Pierce, 1852 ... Barnett and Lewis, 1995

  7. Genome-Wide Analysis of the Expansin Gene Superfamily Reveals Grapevine-Specific Structural and Functional Characteristics

    PubMed Central

    Tornielli, Giovanni Battista; Fasoli, Marianna; Venturini, Luca; Pezzotti, Mario; Zenoni, Sara

    2013-01-01

    Background Expansins are proteins that loosen plant cell walls in a pH-dependent manner, probably by increasing the relative movement among polymers thus causing irreversible expansion. The expansin superfamily (EXP) comprises four distinct families: expansin A (EXPA), expansin B (EXPB), expansin-like A (EXLA) and expansin-like B (EXLB). There is experimental evidence that EXPA and EXPB proteins are required for cell expansion and developmental processes involving cell wall modification, whereas the exact functions of EXLA and EXLB remain unclear. The complete grapevine (Vitis vinifera) genome sequence has allowed the characterization of many gene families, but an exhaustive genome-wide analysis of expansin gene expression has not been attempted thus far. Methodology/Principal Findings We identified 29 EXP superfamily genes in the grapevine genome, representing all four EXP families. Members of the same EXP family shared the same exon–intron structure, and phylogenetic analysis confirmed a closer relationship between EXP genes from woody species, i.e. grapevine and poplar (Populus trichocarpa), compared to those from Arabidopsis thaliana and rice (Oryza sativa). We also identified grapevine-specific duplication events involving the EXLB family. Global gene expression analysis confirmed a strong correlation among EXP genes expressed in mature and green/vegetative samples, respectively, as reported for other gene families in the recently-published grapevine gene expression atlas. We also observed the specific co-expression of EXLB genes in woody organs, and the involvement of certain grapevine EXP genes in berry development and post-harvest withering. Conclusion Our comprehensive analysis of the grapevine EXP superfamily confirmed and extended current knowledge about the structural and functional characteristics of this gene family, and also identified properties that are currently unique to grapevine expansin genes. Our data provide a model for the functional characterization of grapevine gene families by combining phylogenetic analysis with global gene expression profiling. PMID:23614035

  8. Induction of Protective Genes Leads to Islet Survival and Function

    PubMed Central

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

    2011-01-01

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

  9. Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder.

    PubMed

    Wingo, Aliza P; Gibson, Greg

    2015-01-01

    Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD. PMID:25300922

  10. Digestive Organ in the Female Reproductive Tract Borrows Genes from Multiple Organ Systems to Adopt Critical Functions

    PubMed Central

    Meslin, Camille; Plakke, Melissa S.; Deutsch, Aaron B.; Small, Brandon S.; Morehouse, Nathan I.; Clark, Nathan L.

    2015-01-01

    Persistent adaptive challenges are often met with the evolution of novel physiological traits. Although there are specific examples of single genes providing new physiological functions, studies on the origin of complex organ functions are lacking. One such derived set of complex functions is found in the Lepidopteran bursa copulatrix, an organ within the female reproductive tract that digests nutrients from the male ejaculate or spermatophore. Here, we characterized bursa physiology and the evolutionary mechanisms by which it was equipped with digestive and absorptive functionality. By studying the transcriptome of the bursa and eight other tissues, we revealed a suite of highly expressed and secreted gene products providing the bursa with a combination of stomach-like traits for mechanical and enzymatic digestion of the male spermatophore. By subsequently placing these bursa genes in an evolutionary framework, we found that the vast majority of their novel digestive functions were co-opted by borrowing genes that continue to be expressed in nonreproductive tissues. However, a number of bursa-specific genes have also arisen, some of which represent unique gene families restricted to Lepidoptera and may provide novel bursa-specific functions. This pattern of promiscuous gene borrowing and relatively infrequent evolution of tissue-specific duplicates stands in contrast to studies of the evolution of novelty via single gene co-option. Our results suggest that the evolution of complex organ-level phenotypes may often be enabled (and subsequently constrained) by changes in tissue specificity that allow expression of existing genes in novel contexts, such as reproduction. The extent to which the selective pressures encountered in these novel roles require resolution via duplication and sub/neofunctionalization is likely to be determined by the need for specialized reproductive functionality. Thus, complex physiological phenotypes such as that found in the bursa offer important opportunities for understanding the relative role of pleiotropy and specialization in adaptive evolution. PMID:25725432

  11. Functional characterization of GPC-1 genes in hexaploid wheat.

    PubMed

    Avni, Raz; Zhao, Rongrong; Pearce, Stephen; Jun, Yan; Uauy, Cristobal; Tabbita, Facundo; Fahima, Tzion; Slade, Ann; Dubcovsky, Jorge; Distelfeld, Assaf

    2014-02-01

    In wheat, monocarpic senescence is a tightly regulated process during which nitrogen (N) and micronutrients stored pre-anthesis are remobilized from vegetative tissues to the developing grains. Recently, a close connection between senescence and remobilization was shown through the map-based cloning of the GPC (grain protein content) gene in wheat. GPC-B1 encodes a NAC transcription factor associated with earlier senescence and increased grain protein, iron and zinc content, and is deleted or non-functional in most commercial wheat varieties. In the current research, we identified 'loss of function' ethyl methanesulfonate mutants for the two GPC-B1 homoeologous genes; GPC-A1 and GPC-D1, in a hexaploid wheat mutant population. The single gpc-a1 and gpc-d1 mutants, the double gpc-1 mutant and control lines were grown under field conditions at four locations and were characterized for senescence, GPC, micronutrients and yield parameters. Our results show a significant delay in senescence in both the gpc-a1 and gpc-d1 single mutants and an even stronger effect in the gpc-1 double mutant in all the environments tested in this study. The accumulation of total N in the developing grains showed a similar increase in the control and gpc-1 plants until 25 days after anthesis (DAA) but at 41 and 60 DAA the control plants had higher grain N content than the gpc-1 mutants. At maturity, GPC in all mutants was significantly lower than in control plants while grain weight was unaffected. These results demonstrate that the GPC-A1 and GPC-D1 genes have a redundant function and play a major role in the regulation of monocarpic senescence and nutrient remobilization in wheat. PMID:24170335

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

    PubMed Central

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

    2008-01-01

    We have previously described the transcriptional changes that occur in the hippocampal CA1 field of aged rats following a Morris Water Maze (MWM) training paradigm. In this report we proceed with the analysis of the dentate region from the same animals. Animals were first identified as age learning-impaired or age-superior learners when compared to young rats based on their performance in the MWM. Messenger RNA was isolated from the dentate gyrus of each animal to interrogate Affymetrix RAE 230A rat genome microarrays. Microarray profiling identified 1129 genes that were differentially expressed between aged and young rats as a result of aging, and independent of their behavioral training (p<0.005). We applied Ingenuity Pathway Analysis (IPA) algorithms to identify the significant biological processes underlying age-related changes in the dentate gyrus. The most significant functions, as calculated by IPA, included cell movement, cell growth and proliferation, nervous system development and function, cellular assembly and organization, cell morphology and cell death. These significant processes are consistent with age-related changes in neurogenesis, and the neurogenic markers were generally found to be downregulated in senescent animals. In addition, statistical analysis of the different experimental groups of aged animals recognized 85 genes (p<0.005) that were different in the dentate gyrus of aged rats that had learned the MWM when compared to learning impaired and a number of controls for stress, exercise and non-spatial learning. The list of learning-related genes expressed in the dentate adds to the set of genes we previously described in the CA1 region. This long list of genes constitutes a starting tool to elucidating the molecular pathways involved in learning and memory formation. PMID:18234529

  13. Relating Functional Groups to the Periodic Table

    ERIC Educational Resources Information Center

    Struyf, Jef

    2009-01-01

    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.)

  14. Gamma and Related Functions Generalized for Sequences

    ERIC Educational Resources Information Center

    Ollerton, R. L.

    2008-01-01

    Given a sequence g[subscript k] greater than 0, the "g-factorial" product [big product][superscript k] [subscript i=1] g[subscript i] is extended from integer k to real x by generalizing properties of the gamma function [Gamma](x). The Euler-Mascheroni constant [gamma] and the beta and zeta functions are also generalized. Specific examples include…

  15. In vitro gene regulatory networks predict in vivo function of liver

    PubMed Central

    2010-01-01

    Background Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. Results Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. Conclusions The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity. PMID:21073692

  16. Network analysis of neurotransmitter related human kinase genes: possible role of SRC, RAF1, PTK2B?

    PubMed

    Brys, Zoltan; Pluhar, Andras; Kis, Janos Tibor; Buda, Bela; Szabo, Attila

    2013-09-01

    Previous co-expression analysis of human kinase genes highlighted 119 genes in neurotransmitter-related activity (based on Go:Terms). Using a merged interactome dataset, we analyzed the network of these Neurotransmitter Related Human Kinase Genes. Using the full interactome dataset we extended the network and calculating degrees and closeness centralities we identified SRC, MAPK1, RAF1, PTK2B and AKT1 kinase genes as potentially relevant nodes which did not show relevant activity in the original experimental study. As AKT1 and MAPK1 have already been indicated in various neuronal functions, we hypothesize a potential direct or indirect role for SRC, RAF1, PTK2B genes in neurotransmission and in central nervous system signaling processes. PMID:24108181

  17. Molecular Cloning and Functional Expression of the Equine K+ Channel KV11.1 (Ether à Go-Go-Related/KCNH2 Gene) and the Regulatory Subunit KCNE2 from Equine Myocardium

    PubMed Central

    Pedersen, Philip Juul; Thomsen, Kirsten Brolin; Olander, Emma Rie; Hauser, Frank; Tejada, Maria de los Angeles; Poulsen, Kristian Lundgaard; Grubb, Soren; Buhl, Rikke; Calloe, Kirstine; Klaerke, Dan Arne

    2015-01-01

    The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary ? subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tachyarrhythmia and sudden cardiac death—conditions known as congenital or acquired Long QT syndrome (LQTS), respectively. In horses, sudden, unexplained deaths are a well-known problem. We sequenced the cDNA of the KCNH2 and KCNE2 genes using RACE and conventional PCR on mRNA purified from equine myocardial tissue. Equine KV11.1 and KCNE2 cDNA had a high homology to human genes (93 and 88%, respectively). Equine and human KV11.1 and KV11.1/KCNE2 were expressed in Xenopus laevis oocytes and investigated by two-electrode voltage-clamp. Equine KV11.1 currents were larger compared to human KV11.1, and the voltage dependence of activation was shifted to more negative values with V1/2 = -14.2±1.1 mV and -17.3±0.7, respectively. The onset of inactivation was slower for equine KV11.1 compared to the human homolog. These differences in kinetics may account for the larger amplitude of the equine current. Furthermore, the equine KV11.1 channel was susceptible to pharmacological block with terfenadine. The physiological importance of KV11.1 was investigated in equine right ventricular wedge preparations. Terfenadine prolonged action potential duration and the effect was most pronounced at slow pacing. In conclusion, these findings indicate that horses could be disposed to both congenital and acquired LQTS. PMID:26376488

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

    PubMed Central

    Hutchins, James R. A.

    2014-01-01

    The genomic era has enabled research projects that use approaches including genome-scale screens, microarray analysis, next-generation sequencing, and mass spectrometry–based proteomics to discover genes and proteins involved in biological processes. Such methods generate data sets of gene, transcript, or protein hits that researchers wish to explore to understand their properties and functions and thus their possible roles in biological systems of interest. Recent years have seen a profusion of Internet-based resources to aid this process. This review takes the viewpoint of the curious biologist wishing to explore the properties of protein-coding genes and their products, identified using genome-based technologies. Ten key questions are asked about each hit, addressing functions, phenotypes, expression, evolutionary conservation, disease association, protein structure, interactors, posttranslational modifications, and inhibitors. Answers are provided by presenting the latest publicly available resources, together with methods for hit-specific and data set–wide information retrieval, suited to any genome-based analytical technique and experimental species. The utility of these resources is demonstrated for 20 factors regulating cell proliferation. Results obtained using some of these are discussed in more depth using the p53 tumor suppressor as an example. This flexible and universally applicable approach for characterizing experimental hits helps researchers to maximize the potential of their projects for biological discovery. PMID:24723265

  19. Functionally relevant diversity of closely related Nitrospira in activated sludge

    PubMed Central

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

    2014-01-01

    Nitrospira are chemolithoautotrophic nitrite-oxidizing bacteria that catalyse 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 analysed 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 co-aggregation 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 OTUs 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

  20. Gene transfer-mediated functional restoration for irradiated salivary glands.

    PubMed

    Wang, Song Ling; Gao, Run Tao

    2011-01-01

    Radiation therapy for malignant tumours in the head and neck region are inevitably associated with significant long-term injury to the salivary glands, often resulting in salivary gland hypofunction. The subsequent lack of saliva production leads to many functional and quality-of-life problems for affected patients and there is no effective method to eliminating this problem caused by radiation treatments. Although many studies have been done in animal models, the mechanism of this injury in humans is still unclear. In this review, an animal model (miniature pigs) used in irradiated research is mainly discussed. This review also presents the progress made to date on the gene transfer-mediated functional restoration of irradiated salivary glands and the possibilities provided by future interventions to prevent radiation damage to salivary glands. PMID:21734941

  1. Initial characterization of shade avoidance response suggests functional diversity between Populus phytochrome B genes.

    SciTech Connect

    Karve, Abhijit A; Weston, David; Jawdy, Sara; Gunter, Lee E; Allen, Sara M; Yang, Xiaohan; Wullschleger, Stan D; Tuskan, Gerald A

    2012-01-01

    Shade avoidance signaling in higher plants involves perception of the incident red/far-red (R/FR) light by phytochromes and the modulation of downstream transcriptional networks to regulate developmental plasticity in relation to heterogeneous light environments. In this study, we characterized the expression and functional features of Populus phytochrome (PHY) gene family as well as the transcriptional responses of Populus to the changes in R/FR light. Expression data indicated that PHYA is the predominant PHY in the dark grown Populus seedling whereas PHYBs are most abundant in mature tissue types. Out of three Populus PHYs, PHYA is light labile and localized to cytosol in dark whereas both PHYB1 and PHYB2 are light stable and are localized to nucleus in mesophyll protoplasts. When expressed in Arabidopsis, PHYB1 rescued Arabidopsis phyB mutant phenotype whereas PHYB2 did not, suggesting functional diversification between these two gene family members. However, phenotypes of transgenic Populus lines with altered expression of PHYB1, PHYB2 or both and the expression of candidate shade response genes in these transgenic lines suggest that PHYB1 and PHYB2 may have distinct yet overlapping functions. The RNAseq results and analysis of Populus exposed to enriched-FR light indicate that genes associated in cell wall modification and brassinosteroid signaling were induced under far red light. Overall our data indicate that Populus transcriptional responses are at least partially conserved with Arabidopsis.

  2. Allelic variation of polyphenol oxidase (PPO) genes located on chromosomes 2A and 2D and development of functional markers for the PPO genes in common wheat.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyphenol oxidase (PPO) activity is highly related to the undesirable browning of wheat-based end products, especially Asian noodles. Characterization of PPO genes and the development of their functional markers are of great importance for marker-assisted selection in wheat breeding. In the prese...

  3. Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy

    PubMed Central

    Baird, Andrew; Lee, Jisook; Podvin, Sonia; Kurabi, Arwa; Dang, Xitong; Coimbra, Raul; Costantini, Todd; Bansal, Vishal; Eliceiri, Brian P

    2014-01-01

    In humans, esophageal cancer-related gene 4 (ECRG4) is encoded by four exons in the c2orf40 locus of chromosome 2. Translation of ECRG4 messenger ribonucleic acid produces a 148 amino acid-secreted 17 KDa protein that is then processed to 14, ten, eight, six, four, and two KDa peptides, depending on the cell in which the gene is expressed. As hypermethylation at the c2orf40 locus inhibits ECRG4 gene expression in many epithelial cancers, several investigators have speculated that ECRG4 is a candidate tumor suppressor. Indeed, overexpression of ECRG4 inhibits cell proliferation in vitro, but it also has a wide range of effects in vivo beyond its antitumor activity. ECRG4 overexpression affects apoptosis, senescence, cell migration, inflammation, injury, and infection responsiveness. ECRG4 activities also depend on its cellular localization, secretion, and post-translational processing. These cytokine/chemokine-like characteristics argue that ECRG4 is not a traditional candidate tumor suppressor gene, as originally predicted by its downregulation in cancer. We review how insights into the regulation of ECRG4 gene expression, knowledge of its primary structure, and the study of its emerging physiological functions come together to support a much more complex role for ECRG4 at the interface of inflammation, infection, and malignancy. PMID:25580077

  4. Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise.

    PubMed

    Denham, Joshua; O'Brien, Brendan J; Marques, Francine Z; Charchar, Fadi J

    2015-02-15

    Physical exercise has proven cardiovascular benefits, yet there is no clear understanding of the related molecular mechanisms leading to this. Here we determined the beneficial epigenetic effects of exercise after sprint interval training, a form of exercise known to improve cardiometabolic health. We quantified genome-wide leukocyte DNA methylation of 12 healthy young (18-24 yr) men before and after 4 wk (thrice weekly) of sprint interval training using the 450K BeadChip (Illumina) and validated gene expression changes in an extra seven subjects. Exercise increased subjects' cardiorespiratory fitness and maximal running performance, and decreased low-density lipoprotein cholesterol concentration in conjunction with genome-wide DNA methylation changes. Notably, many CpG island and gene promoter regions were demethylated after exercise, indicating increased genome-wide transcriptional changes. Among genes with DNA methylation changes, epidermal growth factor (EGF), a ligand of the epidermal growth factor receptor known to be involved in cardiovascular disease, was demethylated and showed decreased mRNA expression. Additionally, we found that in microRNAs miR-21 and miR-210, gene DNA methylation was altered by exercise causing a cascade effect on the expression of the mature microRNA involved in cardiovascular function. Our findings demonstrate that exercise alters DNA methylation in circulating blood cells in microRNA and protein-coding genes associated with cardiovascular physiology. PMID:25539938

  5. The hedgehog-related gene wrt-5 is essential for hypodermal development in Caenorhabditis elegans.

    PubMed

    Hao, Limin; Aspöck, Gudrun; Bürglin, Thomas R

    2006-02-15

    The Caenorhabditis elegans genome encodes a series of hedgehog-related genes, which are thought to have evolved and diverged from an ancestral Hh gene. They are classified into several families based on their N-terminal domains. Here, we analyze the expression and function of a member of the warthog gene family, wrt-5, that lacks the Hint/Hog domain. wrt-5 is expressed in seam cells, the pharynx, pharyngeal-intestinal valve cells, neurons, neuronal support cells, the excretory cell, and the reproductive system. WRT-5 protein is secreted into the extracellular space during embryogenesis. Furthermore, during larval development, WRT-5 protein is secreted into the pharyngeal lumen and the pharyngeal expression changes in a cyclical manner in phase with the molting cycle. Deletion mutations in wrt-5 cause embryonic lethality, which are temperature sensitive and more severe at 15 degrees C than at 25 degrees C. Animals that hatch exhibit variable abnormal morphology, for example, bagging worms, blistering, molting defects, or Roller phenotypes. We examined hypodermal cell junctions using the AJM-1Colon, two colonsGFP marker in the wrt-5 mutant background and observed cell boundary abnormalities in the arrested embryos. AJM-1Colon, two colonsGFP protein is also misplaced in pharyngeal muscle cells in the absence of WRT-5. In conclusion, we show that wrt-5 is an essential gene that - despite its lack of a Hint domain - has multiple functions in C. elegans and is implicated in cell shape integrity. PMID:16413526

  6. The dystrophin gene and cognitive function in the general population.

    PubMed

    Vojinovic, Dina; Adams, Hieab H H; van der Lee, Sven J; Ibrahim-Verbaas, Carla A; Brouwer, Rutger; van den Hout, Mirjam C G N; Oole, Edwin; van Rooij, Jeroen; Uitterlinden, Andre; Hofman, Albert; van IJcken, Wilfred F J; Aartsma-Rus, Annemieke; van Ommen, GertJan B; Ikram, M Arfan; van Duijn, Cornelia M; Amin, Najaf

    2015-06-01

    The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10(-4)), rs147546024:A>G showed strong association (? = 1.786, P-value = 2.56 × 10(-4)) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (? = -0.465, P-value = 0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values = 0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations. PMID:25227141

  7. The ral gene: a new ras related gene isolated by the use of a synthetic probe.

    PubMed Central

    Chardin, P; Tavitian, A

    1986-01-01

    We synthesized a set of 20-mer oligonucleotides corresponding to a sequence of seven amino acids strictly conserved in all the different ras proteins, from yeast to man, as well as in rho and YPT, two proteins distantly related to p21 ras (approximately 30% amino acid homology). This oligonucleotide probe was used to search for new members of the ras family. We describe here a new ras related gene named ral, isolated from a cDNA library of immortalized simian B-lymphocytes. The ral gene codes for a 206 amino acid protein of expected mol. wt 23.5 kd that shares greater than 50% homology with H-ras, K-ras or N-ras. The GTP binding regions of p21 ras and a C-terminal cysteine involved in membrane anchoring are also present in ral; this strongly suggests that ral is a GTP binding protein with membrane localization. Furthermore, several external regions of p21 ras presumably involved in the interaction with effector, receptor and/or regulatory proteins are highly homologous to the corresponding regions in ral. Therefore some of the proteins that interact with ral might be identical or closely related to those interacting with p21 ras. Images Fig. 2. PMID:3023062

  8. Klotho gene polymorphisms are related to colorectal cancer susceptibility

    PubMed Central

    Liu, Chang; Cui, Wei; Wang, Li; Yan, Lei; Ruan, Xinjian; Liu, Yanfang; Jia, Xiaoyan; Zhang, Xia

    2015-01-01

    Aim: The purpose of this study was to investigate the relationship of Klotho gene G-395A and C1818T polymorphisms with colorectal cancer (CRC) susceptibility. Methods: 125 CRC patients and 125 controls were enrolled in the study. G-395A and C1818T polymorphisms were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Haploview software was utilized to conduct linkage disequilibrium and haplotype analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to analyze the correlation of genotypes and haplotypes with CRC susceptibility. Results: AA and GA genotypes of G-395A polymorphisms were related with CRC risk (AA: OR = 4.161, 95% CI = 1.437-12.053; GA: OR = 1.958, 95% CI = 1.133-3.385). The frequency of A allele was much higher in case group, compared with controls (31.2% vs.17.6%) and the value of OR AND 95% CI suggested that A allele served as a risk factor for CRC (OR = 2.123, 95% CI = 1.393-3.236). Haplotypes analysis indicated that A-C and A-T haplotypes were significantly associated with risk of CRC (OR = 1.822, 95% CI = 1.124-2.954; OR = 2.877, 95% CI = 1.340-6.176). Conclusion: G-395A polymorphism of Klotho gene could increase the risk of CRC. PMID:26261651

  9. Data Integration and Applications of Functional Gene Networks in Drosophila Melanogaster

    ERIC Educational Resources Information Center

    Costello, James Christopher

    2009-01-01

    Understanding the function of every gene in the genome is a central goal in the biological sciences. This includes full characterization of a genes phenotypic effects, molecular interactions, the evolutionary forces that shape its function(s), and how these functions interrelate. Despite a long history and considerable effort to understand all…

  10. DEPDC1 is a novel cell cycle related gene that regulates mitotic progression

    PubMed Central

    Mi, Yan; Zhang, Chundong; Bu, Youquan; Zhang, Ying; He, Longxia; Li, Hongxia; Zhu, Huifang; Li, Yi; Lei, Yunlong; Zhu, Jiang

    2015-01-01

    DEPDC1 is a recently identified novel tumor-related gene that is upregulated in several types of cancer and contributes to tumorigenesis. In this study, we have investigated the expression pattern and functional implications of DEPDC1 during cell cycle progression. Expression studies using synchronized cells demonstrated that DEPDC1 is highly expressed in the mitotic phase of the cell cycle. Immunofluorescence assays showed that DEPDC1 is predominantly localized in the nucleus during interphase and is redistributed into the whole cell upon nuclear membrane breakdown in metaphase. Subsequently, siRNA-mediated knockdown of DEPDC1 caused a significant mitotic arrest. Moreover, knockdown of DEPDC1 resulted in remarkable mitotic defects such as abnormal multiple nuclei and multipolar spindle structures accompanied by the upregulation of the A20 gene as well as several cell cycle-related genes such as CCNB1 and CCNB2. Taken together, our current observations strongly suggest that this novel cancerous gene, DEPDC1, plays a pivotal role in the regulation of proper mitotic progression. [BMB Reports 2015; 48(7): 413-418] PMID:25902835

  11. Tracing evolutionary relicts of positive selection on eight malaria-related immune genes in mammals.

    PubMed

    Huang, Bing-Hong; Liao, Pei-Chun

    2015-07-01

    Plasmodium-induced malaria widely infects primates and other mammals. Multiple past studies have revealed that positive selection could be the main evolutionary force triggering the genetic diversity of anti-malaria resistance-associated genes in human or primates. However, researchers focused most of their attention on the infra-generic and intra-specific genome evolution rather than analyzing the complete evolutionary history of mammals. Here we extend previous research by testing the evolutionary link of natural selection on eight candidate genes associated with malaria resistance in mammals. Three of the eight genes were detected to be affected by recombination, including TNF-?, iNOS and DARC. Positive selection was detected in the rest five immunogenes multiple times in different ancestral lineages of extant species throughout the mammalian evolution. Signals of positive selection were exposed in four malaria-related immunogenes in primates: CCL2, IL-10, HO1 and CD36. However, selection signals of G6PD have only been detected in non-primate eutherians. Significantly higher evolutionary rates and more radical amino acid replacement were also detected in primate CD36, suggesting its functional divergence from other eutherians. Prevalent positive selection throughout the evolutionary trajectory of mammalian malaria-related genes supports the arms race evolutionary hypothesis of host genetic response of mammalian immunogenes to infectious pathogens. PMID:25201904

  12. Autoinducer-2 signaling is involved in regulation of stress-related genes of Deinococcus radiodurans.

    PubMed

    Lin, Lin; Li, Tao; Dai, Shang; Yu, Jiangliu; Chen, Xiuqin; Wang, Liangyan; Wang, Yunguang; Hua, Yuejin; Tian, Bing

    2016-01-01

    Autoinducer-2 (AI-2) serves as a quorum-sensing signaling molecule that mediates both intraspecies and interspecies communication among bacteria, and plays critical roles in regulating various bacterial behaviors. In the present study, we investigated the functions of AI-2 signaling in the extremophilic bacterium Deinococcus radiodurans R1 by construction of the LuxS gene disruption mutant, survival phenotype assay and gene transcription assay. The gene mutant (DR?LuxS), which was unable to produce AI-2, was significantly more sensitive to both gamma radiation and H2O2 compared with the wild-type strain. Addition of the wild-type-derived spent medium into the cell culture of DR?LuxS fully restored the radioresistance of D. radiodurans. A higher level of reactive oxygen species accumulated in the mutant compared with the wild type under normal or oxidative stress. Quantitative real-time PCR assays showed that transcriptional levels of stress-related proteins, including catalase, extracellular nuclease, Dps-1 and ABC transporters, were decreased in DR?LuxS, indicating that AI-2 is involved in regulation of stress-related genes of D. radiodurans. Hence, AI-2 signaling may contribute to the extreme resistance of D. radiodurans to radiation and oxidative stresses. PMID:26510931

  13. Large-scale identification of encystment-related proteins and genes in Pseudourostyla cristata

    PubMed Central

    Gao, Xiuxia; Chen, Fenfen; Niu, Tao; Qu, Ruidan; Chen, Jiwu

    2015-01-01

    The transformation of a ciliate into cyst is an advance strategy against an adverse situation. However, the molecular mechanism for the encystation of free-living ciliates is poorly understood. A large-scale identification of the encystment-related proteins and genes in ciliate would provide us with deeper insights into the molecular mechanisms for the encystations of ciliate. We identified the encystment-related proteins and genes in Pseudourostyla cristata with shotgun LC-MS/MS and scale qRT-PCR, respectively, in this report. A total of 668 proteins were detected in the resting cysts, 102 of these proteins were high credible proteins, whereas 88 high credible proteins of the 724 total proteins were found in the vegetative cells. Compared with the vegetative cell, 6 specific proteins were found in the resting cyst. However, the majority of high credible proteins in the resting cyst and the vegetative cell were co-expressed. We compared 47 genes of the co-expressed proteins with known functions in both the cyst and the vegetative cell using scale qRT-PCR. Twenty-seven of 47 genes were differentially expressed in the cyst compared with the vegetative cell. In our identifications, many uncharacterized proteins were also found. These results will help reveal the molecular mechanism for the formation of cyst in ciliates. PMID:26079518

  14. RNA-mediated silencing in Algae: biological roles and tools for analysis of gene function.

    PubMed

    Cerutti, Heriberto; Ma, Xinrong; Msanne, Joseph; Repas, Timothy

    2011-09-01

    Algae are a large group of aquatic, typically photosynthetic, eukaryotes that include species from very diverse phylogenetic lineages, from those similar to land plants to those related to protist parasites. The recent sequencing of several algal genomes has provided insights into the great complexity of these organisms. Genomic information has also emphasized our lack of knowledge of the functions of many predicted genes, as well as the gene regulatory mechanisms in algae. Core components of the machinery for RNA-mediated silencing show widespread distribution among algal lineages, but they also seem to have been lost entirely from several species with relatively small nuclear genomes. Complex sets of endogenous small RNAs, including candidate microRNAs and small interfering RNAs, have now been identified by high-throughput sequencing in green, red, and brown algae. However, the natural roles of RNA-mediated silencing in algal biology remain poorly understood. Limited evidence suggests that small RNAs may function, in different algae, in defense mechanisms against transposon mobilization, in responses to nutrient deprivation and, possibly, in the regulation of recently evolved developmental processes. From a practical perspective, RNA interference (RNAi) is becoming a promising tool for assessing gene function by sequence-specific knockdown. Transient gene silencing, triggered with exogenously synthesized nucleic acids, and/or stable gene repression, involving genome-integrated transgenes, have been achieved in green algae, diatoms, yellow-green algae, and euglenoids. The development of RNAi technology in conjunction with system level "omics" approaches may provide the tools needed to advance our understanding of algal physiological and metabolic processes. PMID:21803865

  15. Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines

    PubMed Central

    2011-01-01

    Background Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. Results In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB-siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. Conclusions The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine. PMID:22051105

  16. Identification of genes and pathways related to lipopolysaccharide signaling in duckling spleens.

    PubMed

    Deng, B; Yu, T; Liu, W; Ye, S Q; Wang, L X; Yang, Y; Gong, P; Ran, Z P; Huang, H J; Wen, J H

    2015-01-01

    Lipopolysaccharide (LPS), the major component of the outer cell wall of Gram-negative bacteria, activates the immune system and threatens the health of livestock and poultry. However, little is known about the genes and pathways involved in the immune response of ducklings to LPS. To elucidate the genes involved in the response of 7-day-old duckling spleens treated with LPS, RNA from LPS-treated and control duckling spleens was analyzed by RNA-Seq. The results showed 11,095 and 10,840 genes with >10 clean reads in the LPS-treated and control groups, respectively. Among these genes, 89 were differentially expressed (log2 ratio ? 1, P ? 0.01, false discovery rate ? 0.001); 67 of these were upregulated and 22 were downregulated in the LPS-treated group compared to the control. GO and GO-rich analysis showed that differentially expressed genes were enriched in 13 functional categories (P < 0.05). Pathway analysis and pathway richness analysis showed that differentially expressed genes were enriched in six pathway categories (P < 0.05). Further analysis showed that some immune system-related signaling pathways, such as the hematopoietic cell lineage, Toll-like receptor signaling pathway, T cell receptor signaling pathway, T cell receptor signaling pathway, complement and coagulation cascades, antigen processing and presentation, and chemokine signaling pathway, are active during the immune response. To confirm the RNA-Seq results, we detected CCL4, LBP, CD71, and STEAP3 expression using real-time PCR analysis, and the results were consistent with the RNA-Seq results. Our results provide new information on the genes involved in the immune response of duckling spleens to LPS. PMID:26681226

  17. Intron features of key functional genes mediating nitrogen metabolism in marine phytoplankton

    E-print Network

    Ward, Bess

    Intron features of key functional genes mediating nitrogen metabolism in marine phytoplankton on the evolutionary history of genes and organisms. The number and frequency of introns vary widely in the small in sequences of functional genes of phytoplankton, both in published genomes and in sequences obtained from

  18. Association of polymorphisms in natural killer cell-related genes with preterm birth.

    PubMed

    Harmon, Quaker E; Engel, Stephanie M; Olshan, Andrew F; Moran, Thomas; Stuebe, Alison M; Luo, Jingchun; Wu, Michael C; Avery, Christy L

    2013-10-15

    Inflammation is implicated in preterm birth, but genetic studies of inflammatory genes have yielded inconsistent results. Maternal DNA from 1,646 participants in the Pregnancy, Infection, and Nutrition Cohort, enrolled in Orange and Wake counties, North Carolina (1995-2005), were genotyped for 432 tag single-nucleotide polymorphisms (SNPs) in 30 candidate genes. Gene-level and SNP associations were modeled within strata of genetic ancestry. Six genes were associated with preterm birth among European Americans: interleukin 12A (IL12A); colony-stimulating factor 2 (CSF2); interferon ? receptor 2 (IFNGR2); killer cell immunoglobulin-like receptor, three domain, long cytoplasmic tail, 2 (KIR3DL2); interleukin 4 (IL4); and interleukin 13 (IL13). Of these, relatively strong single-SNP associations were seen in IFNGR2 and KIR3DL2. Among the 4 genes related to natural killer cell function, 2 (IL12A and CSF2) were consistently associated with reduced risk of prematurity for both European and African Americans. SNPs tagging a locus control region for IL4 and IL13 were associated with an increased risk of spontaneous preterm birth for European Americans (rs3091307; risk ratio = 1.9; 95% confidence interval: 1.4, 2.5). Although gene-level associations were detected only in European Americans, single-SNP associations among European and African Americans were often similar in direction, though estimated with less precision among African Americans. In conclusion, we identified novel associations between variants in the natural killer cell immune pathway and prematurity in this biracial US population. PMID:23982189

  19. Gene × Environment Determinants of Stress- and Anxiety-Related Disorders.

    PubMed

    Sharma, Sumeet; Powers, Abigail; Bradley, Bekh; Ressler, Kerry J

    2016-01-01

    The burgeoning field of gene-by-environment (G×E) interactions has revealed fascinating biological insights, particularly in the realm of stress-, anxiety-, and depression-related disorders. In this review we present an integrated view of the study of G×E interactions in stress and anxiety disorders, including the evolution of genetic association studies from genetic epidemiology to contemporary large-scale genome-wide association studies and G×E studies. We convey the importance of consortia efforts and collaboration to gain the large sample sizes needed to move the field forward. Finally, we discuss several robust and well-reproduced G×E interactions and demonstrate how epidemiological identification of G×E interactions has naturally led to a plethora of basic research elucidating the mechanisms of high-impact genetic variants. PMID:26442668

  20. Gene patents related to common diseases of the eye.

    PubMed

    Sahebjada, Srujana; Cantsileris, Stuart; Baird, Paul N

    2011-12-01

    Visual impairment and blindness impose substantial morbidity and premature mortality on the population. The direct costs for vision disorders have been shown to be more than the cost of coronary heart disease, stroke, arthritis or depression and were estimated to be $9.85 billion in 2004 in Australia. Hence it is important to identify the causes of common eye diseases and understand their aetiology which in turn would allow determination of better management strategies and treatment options. Age related Macular Degeneration, Cataract, Diabetic Retinopathy, Glaucoma and uncorrected refractive errors represent the majority of the visual impairment and blindness in Australia and various parts of the world. This article reviews the gene patents available for these eye conditions and highlights the important discoveries that have so far contributed to our understanding of these diseases and provides valuable information as to where research will be heading in the future. PMID:21867478

  1. Charge transport in cancer-related genes and early carcinogenesis

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

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

  2. Impact of the ADHD-susceptibility gene CDH13 on development and function of brain networks.

    PubMed

    Rivero, Olga; Sich, Sarah; Popp, Sandy; Schmitt, Angelika; Franke, Barbara; Lesch, Klaus-Peter

    2013-06-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common, early onset and enduring neuropsychiatric disorder characterized by developmentally inappropriate inattention, hyperactivity, increased impulsivity and motivational/emotional dysregulation with similar prevalence rates throughout different cultural settings. Persistence of ADHD into adulthood is associated with considerable risk for co-morbidities such as depression and substance use disorder. Although the substantial heritability of ADHD is well documented the etiology is characterized by a complex coherence of genetic and environmental factors rendering identification of risk genes difficult. Genome-wide linkage as well as single nucleotide polymorphism (SNP) and copy-number variant (CNV) association scans recently allow to reliably define aetiopathogenesis-related genes. A considerable number of novel ADHD risk genes implicate biological processes involved in neurite outgrowth and axon guidance. Here, we focus on the gene encoding Cadherin-13 (CDH13), a cell adhesion molecule which was replicably associated with liability to ADHD and related neuropsychiatric conditions. Based on its unique expression pattern in the brain, we discuss the molecular structure and neuronal mechanisms of Cadherin-13 in relation to other cadherins and the cardiovascular system. An appraisal of various Cadherin-13-modulated signaling pathways impacting proliferation, migration and connectivity of specific neurons is also provided. Finally, we develop an integrative hypothesis of the mechanisms in which Cadherin-13 plays a central role in the regulation of brain network development, plasticity and function. The review concludes with emerging concepts about alterations in Cadherin-13 signaling contributing to the pathophysiology of neurodevelopmental disorders. PMID:22795700

  3. The repression of cell wall- and plastid-related genes and the induction of defense-related genes in rice plants infected with Rice dwarf virus.

    PubMed

    Shimizu, Takumi; Satoh, Kouji; Kikuchi, Shoshi; Omura, Toshihiro

    2007-03-01

    An analysis, using microarrays, of gene expression in rice plants infected with Rice dwarf virus revealed significant decreases in levels of expression of genes that are involved in the formation of cell walls, reflecting the stunted growth of diseased plants. The expression of plastid-related genes also was suppressed, as anticipated from the white chlorotic appearance of infected leaves. By contrast, the expression of defense- and stress-related genes was enhanced after viral infection. These results suggest that virus-infected rice plants attempt to survive viral infection and replication by raising the levels of expression of defense- and stress-related genes while suppressing the expression of genes required for the elongation of cells and photosynthesis. PMID:17378427

  4. Integrable pseudopotentials related to generalized hypergeometric functions

    E-print Network

    Alexander Odesskii; Vladimir Sokolov

    2008-05-12

    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.

  5. Revisiting Key Schedule's Diffusion In Relation With Round Function's Diffusion

    E-print Network

    International Association for Cryptologic Research (IACR)

    Revisiting Key Schedule's Diffusion In Relation With Round Function's Diffusion Jialin Huang that the key schedules poorly distribute key bits in the diffusion path of round function. This reminds us of the importance of the diffusion's relation between key schedule and round function. We present new cryptanalysis

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

    E-print Network

    Burke, John M.

    Molecular Evolution of Candidate Genes for Crop-Related Traits in Sunflower (Helianthus annuus L-related traits in sunflower. These genes, which were identified based on homology to genes of known effect of cultivated sunflower, were then sequenced from a panel of wild sunflower accessions an outgroup. These data

  7. Functional relationship among TATA sequences, gene induction and transcription initiation in the beta-galactosidase, LAC4, gene from Kluyveromyces lactis.

    PubMed

    Ficca, A G; Hollenberg, C P

    1989-04-01

    In the 5' non-coding region of the beta-galactosidase, LAC4, gene of Kluyveromyces lactis, three TATA-like sequences are present at -230, -170 and -142 from the ATG translation start site. By means of deletion mutations in the TATA region, at least two of these TATA sequences, those at -230 and -142, were shown to be required for normal gene expression. Evidence is presented for a functional hierarchy and cooperation between these TATA sequences. The deletion or a change in the position of the TATA sequences affects both beta-galactosidase induction and the location of RNA initiation sites. The TATA sequence at -230 alone is sufficient for correct gene induction when it is moved to a position 41 bp from the major RNA initiation sites located around -110; the -142 TATA alone contributes only partly to gene induction. We suggest a functional distinction between these two related regulatory sequences. This functional distinction might be established by sequence differences and/or targets of unlike specific DNA binding protein(s). A conformational analysis of the LAC4 promoter showed that under torsional stress the functional elements UAS, TATA boxes RNA initiation sites and ATG can be detected as P1-sensitive sites. Possible functions of DNA structural alterations on gene expression are discussed. PMID:2546684

  8. PainNetworks: A web-based resource for the visualisation of pain-related genes in the context of their network associations

    PubMed Central

    Perkins, James R.; Lees, Jonathan; Antunes-Martins, Ana; Diboun, Ilhem; McMahon, Stephen B.; Bennett, David L.H.; Orengo, Christine

    2013-01-01

    Hundreds of genes are proposed to contribute to nociception and pain perception. Historically, most studies of pain-related genes have examined them in isolation or alongside a handful of other genes. More recently the use of systems biology techniques has enabled us to study genes in the context of the biological pathways and networks in which they operate. Here we describe a Web-based resource, available at http://www.PainNetworks.org. It integrates interaction data from various public databases with information on known pain genes taken from several sources (eg, The Pain Genes Database) and allows the user to examine a gene (or set of genes) of interest alongside known interaction partners. This information is displayed by the resource in the form of a network. The user can enrich these networks by using data from pain-focused gene expression studies to highlight genes that change expression in a given experiment or pairs of genes showing correlated expression patterns across different experiments. Genes in the networks are annotated in several ways including biological function and drug binding. The Web site can be used to find out more about a gene of interest by looking at the function of its interaction partners. It can also be used to interpret the results of a functional genomics experiment by revealing putative novel pain-related genes that have similar expression patterns to known pain-related genes and by ranking genes according to their network connections with known pain genes. We expect this resource to grow over time and become a valuable asset to the pain community. PMID:24036287

  9. Functional Gene Composition, Diversity and Redundancy in Microbial Stream Biofilm Communities

    PubMed Central

    Dopheide, Andrew; Lear, Gavin; He, Zhili; Zhou, Jizhong; Lewis, Gillian D.

    2015-01-01

    We surveyed the functional gene composition and diversity of microbial biofilm communities in 18 New Zealand streams affected by different types of catchment land use, using a comprehensive functional gene array, GeoChip 3.0. A total of 5,371 nutrient cycling and energy metabolism genes within 65 gene families were detected among all samples (342 to 2,666 genes per stream). Carbon cycling genes were most common, followed by nitrogen cycling genes, with smaller proportions of sulphur, phosphorus cycling and energy metabolism genes. Samples from urban and native forest streams had the most similar functional gene composition, while samples from exotic forest and rural streams exhibited the most variation. There were significant differences between nitrogen and sulphur cycling genes detected in native forest and urban samples compared to exotic forest and rural samples, attributed to contrasting proportions of nitrogen fixation, denitrification, and sulphur reduction genes. Most genes were detected only in one or a few samples, with only a small minority occurring in all samples. Nonetheless, 42 of 65 gene families occurred in every sample and overall proportions of gene families were similar among samples from contrasting streams. This suggests the existence of functional gene redundancy among different stream biofilm communities despite contrasting taxonomic composition. PMID:25849814

  10. The retinoid-related orphan receptor alpha (RORA) gene and fear-related psychopathology

    PubMed Central

    Miller, Mark W.; Wolf, Erika J.; Logue, Mark W.; Baldwin, Clinton T.

    2013-01-01

    Background This study followed on findings from a recent genome-wide association study of PTSD that implicated the retinoid-related orphan receptor alpha (RORA) gene (Logue et al, 2012) by examining its relationship to broader array of disorders. Methods Using data from the same cohort (N = 540), we analyzed patterns of association between 606 single nucleotide polymorphisms (SNPs) spanning the RORA gene and comorbidity factors termed fear, distress (i.e., internalizing factors) and externalizing. Results Results showed that rs17303244 was associated with the fear component of internalizing (i.e., defined by symptoms of panic, agoraphobia, specific phobia, and obsessive-compulsive disorder) at a level of significance that withstood correction for gene-wide multiple testing. Limitations The primary limitations were the modest size of the cohort and the absence of a replication sample. Conclusions Results add to a growing literature implicating the RORA gene in a wide range of neuropsychiatric disorders and offer new insight into possible molecular mechanisms of the effects of traumatic stress on the brain and the role of genetic factors in those processes. PMID:24007783

  11. Estrogen-related receptor {alpha} modulates the expression of adipogenesis-related genes during adipocyte differentiation

    SciTech Connect

    Ijichi, Nobuhiro; Ikeda, Kazuhiro; Horie-Inoue, Kuniko; Yagi, Ken; Okazaki, Yasushi; Inoue, Satoshi . E-mail: INOUE-GER@h.u-tokyo.ac.jp

    2007-07-06

    Estrogen-related receptor {alpha} (ERR{alpha}) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue. However, the physiological role of ERR{alpha} in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERR{alpha} and ERR{alpha}-related transcriptional coactivators, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) coactivator-1{alpha} (PGC-1{alpha}) and PGC-1{beta}, can be up-regulated in 3T3-L1 preadipocytes at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. Gene knockdown by ERR{alpha}-specific siRNA results in mRNA down-regulation of fatty acid binding protein 4, PPAR{gamma}, and PGC-1{alpha} in 3T3-L1 cells in the adipogenesis medium. ERR{alpha} and PGC-1{beta} mRNA expression can be also up-regulated in another preadipocyte lineage DFAT-D1 cells and a pluripotent mesenchymal cell line C3H10T1/2 under the differentiation condition. Furthermore, stable expression of ERR{alpha} in 3T3-L1 cells up-regulates adipogenic marker genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These results suggest that ERR{alpha} may play a critical role in adipocyte differentiation by modulating the expression of various adipogenesis-related genes.

  12. Integrating biological knowledge based on functional annotations for biclustering of gene expression data.

    PubMed

    Nepomuceno, Juan A; Troncoso, Alicia; Nepomuceno-Chamorro, Isabel A; Aguilar-Ruiz, Jesús S

    2015-05-01

    Gene expression data analysis is based on the assumption that co-expressed genes imply co-regulated genes. This assumption is being reformulated because the co-expression of a group of genes may be the result of an independent activation with respect to the same experimental condition and not due to the same regulatory regime. For this reason, traditional techniques are recently being improved with the use of prior biological knowledge from open-access repositories together with gene expression data. Biclustering is an unsupervised machine learning technique that searches patterns in gene expression data matrices. A scatter search-based biclustering algorithm that integrates biological information is proposed in this paper. In addition to the gene expression data matrix, the input of the algorithm is only a direct annotation file that relates each gene to a set of terms from a biological repository where genes are annotated. Two different biological measures, FracGO and SimNTO, are proposed to integrate this information by means of its addition to-be-optimized fitness function in the scatter search scheme. The measure FracGO is based on the biological enrichment and SimNTO is based on the overlapping among GO annotations of pairs of genes. Experimental results evaluate the proposed algorithm for two datasets and show the algorithm performs better when biological knowledge is integrated. Moreover, the analysis and comparison between the two different biological measures is presented and it is concluded that the differences depend on both the data source and how the annotation file has been built in the case GO is used. It is also shown that the proposed algorithm obtains a greater number of enriched biclusters than other classical biclustering algorithms typically used as benchmark and an analysis of the overlapping among biclusters reveals that the biclusters obtained present a low overlapping. The proposed methodology is a general-purpose algorithm which allows the integration of biological information from several sources and can be extended to other biclustering algorithms based on the optimization of a merit function. PMID:25843807

  13. Estrogen-Related Receptor ? (ERR?) and ERR? Are Essential Coordinators of Cardiac Metabolism and Function

    PubMed Central

    Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

    2015-01-01

    Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor ? (ERR?) and ERR? are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERR? and ERR? together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERR? and ERR? influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERR? and cardiac ERR? develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

  14. Inferring mouse gene functions from genomic-scale data using a combined functional network/classification strategy

    PubMed Central

    Kim, Wan Kyu; Krumpelman, Chase; Marcotte, Edward M

    2008-01-01

    The complete set of mouse genes, as with the set of human genes, is still largely uncharacterized, with many pieces of experimental evidence accumulating regarding the activities and expression of the genes, but the majority of genes as yet still of unknown function. Within the context of the MouseFunc competition, we developed and applied two distinct large-scale data mining approaches to infer the functions (Gene Ontology annotations) of mouse genes from experimental observations from available functional genomics, proteomics, comparative genomics, and phenotypic data. The two strategies — the first using classifiers to map features to annotations, the second propagating annotations from characterized genes to uncharacterized genes along edges in a network constructed from the features — offer alternative and possibly complementary approaches to providing functional annotations. Here, we re-implement and evaluate these approaches and their combination for their ability to predict the proper functional annotations of genes in the MouseFunc data set. We show that, when controlling for the same set of input features, the network approach generally outperformed a naïve Bayesian classifier approach, while their combination offers some improvement over either independently. We make our observations of predictive performance on the MouseFunc competition hold-out set, as well as on a ten-fold cross-validation of the MouseFunc data. Across all 1,339 annotated genes in the MouseFunc test set, the median predictive power was quite strong (median area under a receiver operating characteristic plot of 0.865 and average precision of 0.195), indicating that a mining-based strategy with existing data is a promising path towards discovering mammalian gene functions. As one product of this work, a high-confidence subset of the functional mouse gene network was produced — spanning >70% of mouse genes with >1.6 million associations — that is predictive of mouse (and therefore often human) gene function and functional associations. The network should be generally useful for mammalian gene functional analyses, such as for predicting interactions, inferring functional connections between genes and pathways, and prioritizing candidate genes. The network and all predictions are available on the worldwide web. PMID:18613949

  15. Adeno-associated virus 9 mediated FKRP gene therapy restores functional glycosylation of ?-dystroglycan and improves muscle functions.

    PubMed

    Xu, Lei; Lu, Pei Juan; Wang, Chi-Hsien; Keramaris, Elizabeth; Qiao, Chunping; Xiao, Bin; Blake, Derek J; Xiao, Xiao; Lu, Qi Long

    2013-10-01

    Mutations in the FKRP gene are associated with a wide range of muscular dystrophies from mild limb-girdle muscular dystrophy (LGMD) 2I to severe Walker-Warburg syndrome and muscle-eye-brain disease. The characteristic biochemical feature of these diseases is the hypoglycosylation of ?-dystroglycan (?-DG). Currently there is no effective treatment available. In this study, we examined the adeno-associated virus serotype 9 vector (AAV9)-mediated gene therapy in the FKRP mutant mouse model with a proline to leucine missense mutation (P448L). Our results showed that intraperitoneal administration of AAV9-FKRP resulted in systemic FKRP expression in all striated muscles examined with the highest levels in cardiac muscle. Consistent with our previous observations, FKRP protein is localized in the Golgi apparatus in myofibers. Expression of FKRP consequently restored functional glycosylation of ?-DG in the skeletal and cardiac muscles. Significant improvement in dystrophic pathology, serum creatine kinase levels and muscle function was observed. Only limited FKRP transgene expression was detected in kidney and liver with no detectable toxicity. Our results provided evidence for the utility of AAV-mediated gene replacement therapy for FKRP-related muscular dystrophies. PMID:23817215

  16. Coexpression-Based Clustering of Arabidopsis Root Genes Predicts Functional Modules in Early Phosphate Deficiency Signaling1[C][W

    PubMed Central

    Lin, Wen-Dar; Liao, Ya-Yun; Yang, Thomas J.W.; Pan, Chao-Yu; Buckhout, Thomas J.; Schmidt, Wolfgang

    2011-01-01

    Phosphate (Pi) deficiency triggers the differential expression of a large set of genes, which communally adapt the plant to low Pi bioavailability. To infer functional modules in early transcriptional responses to Pi deficiency, we conducted time-course microarray experiments and subsequent coexpression-based clustering of Pi-responsive genes by pairwise comparison of genes against a customized database. Three major clusters, enriched in genes putatively functioning in transcriptional regulation, root hair formation, and developmental adaptations, were predicted from this analysis. Validation of gene expression by quantitative reverse transcription-PCR revealed that transcripts from randomly selected genes were robustly induced within the first hour after transfer to Pi-deplete medium. Pectin-related processes were among the earliest and most robust responses to Pi deficiency, indicating that cell wall alterations are critical in the early transcriptional response to Pi deficiency. Phenotypical analysis of homozygous mutants defective in the expression of genes from the root hair cluster revealed eight novel genes involved in Pi deficiency-induced root hair elongation. The plants responded rapidly to Pi deficiency by the induction of a subset of transcription factors, followed by a repression of genes involved in cell wall alterations. The combined results provide a novel, integrated view at a systems level of the root responses that acclimate Arabidopsis (Arabidopsis thaliana) to suboptimal Pi levels. PMID:21248074

  17. Drosophila tufted is a gain-of-function allele of the proneural gene amos.

    PubMed Central

    Lai, Eric C

    2003-01-01

    Tufted is a classical Drosophila mutant characterized by a large number of ectopic mechanosensory bristles on the dorsal mesothorax. Unlike other ectopic bristle mutants, Tufted is epistatic to achaete and scute, the proneural genes that normally control the development of these sensory organs. In this report, I present genetic and molecular evidence that Tufted is a gain-of-function allele of the proneural gene amos that ectopically activates mechanosensory neurogenesis. I also systematically examine the ability of the various proneural bHLH proteins to cross-activate each other and find that their ability to do so is in general relatively limited, despite their common ability to induce the formation of mechanosensory bristles. This phenomenon seems instead to be related to their shared ability to activate Asense and Senseless. PMID:12702685

  18. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P. (Knoxville, TN)

    1998-01-01

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  19. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P. (Knoxville, TN)

    2000-06-27

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  20. Functional Genomic, Biochemical, and Genetic Characterization of the Salmonella pduO Gene, an ATP:Cob(I)alamin Adenosyltransferase Gene

    PubMed Central

    Johnson, Celeste L. V.; Pechonick, Edith; Park, Sanghee D.; Havemann, Gregory D.; Leal, Nicole A.; Bobik, Thomas A.

    2001-01-01

    Salmonella enterica degrades 1,2-propanediol by a pathway dependent on coenzyme B12 (adenosylcobalamin [AdoCb1]). Previous studies showed that 1,2-propanediol utilization (pdu) genes include those for the conversion of inactive cobalamins, such as vitamin B12, to AdoCbl. However, the specific genes involved were not identified. Here we show that the pduO gene encodes a protein with ATP:cob(I)alamin adenosyltransferase activity. The main role of this protein is apparently the conversion of inactive cobalamins to AdoCbl for 1,2-propanediol degradation. Genetic tests showed that the function of the pduO gene was partially replaced by the cobA gene (a known ATP:corrinoid adenosyltransferase) but that optimal growth of S. enterica on 1,2-propanediol required a functional pduO gene. Growth studies showed that cobA pduO double mutants were unable to grow on 1,2-propanediol minimal medium supplemented with vitamin B12 but were capable of growth on similar medium supplemented with AdoCbl. The pduO gene was cloned into a T7 expression vector. The PduO protein was overexpressed, partially purified, and, using an improved assay procedure, shown to have cob(I)alamin adenosyltransferase activity. Analysis of the genomic context of genes encoding PduO and related proteins indicated that particular adenosyltransferases tend to be specialized for particular AdoCbl-dependent enzymes or for the de novo synthesis of AdoCbl. Such analyses also indicated that PduO is a bifunctional enzyme. The possibility that genes of unknown function proximal to adenosyltransferase homologues represent previously unidentified AdoCbl-dependent enzymes is discussed. PMID:11160088

  1. A Genome-Wide Gene Function Prediction Resource for Drosophila melanogaster

    PubMed Central

    Yan, Han; Venkatesan, Kavitha; Beaver, John E.; Klitgord, Niels; Yildirim, Muhammed A.; Hao, Tong; Hill, David E.; Cusick, Michael E.; Perrimon, Norbert; Roth, Frederick P.; Vidal, Marc

    2010-01-01

    Predicting gene functions by integrating large-scale biological data remains a challenge for systems biology. Here we present a resource for Drosophila melanogaster gene function predictions. We trained function-specific classifiers to optimize the influence of different biological datasets for each functional category. Our model predicted GO terms and KEGG pathway memberships for Drosophila melanogaster genes with high accuracy, as affirmed by cross-validation, supporting literature evidence, and large-scale RNAi screens. The resulting resource of prioritized associations between Drosophila genes and their potential functions offers a guide for experimental investigations. PMID:20711346

  2. Functional divergence in tandemly duplicated Arabidopsis thaliana trypsin inhibitor genes.

    PubMed Central

    Clauss, M J; Mitchell-Olds, T

    2004-01-01

    In multigene families, variation among loci and alleles can contribute to trait evolution. We explored patterns of functional and genetic variation in six duplicated Arabidopsis thaliana trypsin inhibitor (ATTI) loci. We demonstrate significant variation in constitutive and herbivore-induced transcription among ATTI loci that show, on average, 65% sequence divergence. Significant variation in ATTI expression was also found between two molecularly defined haplotype classes. Population genetic analyses for 17 accessions of A. thaliana showed that six ATTI loci arranged in tandem within 10 kb varied 10-fold in nucleotide diversity, from 0.0009 to 0.0110, and identified a minimum of six recombination events throughout the tandem array. We observed a significant peak in nucleotide and indel polymorphism spanning ATTI loci in the interior of the array, due primarily to divergence between the two haplotype classes. Significant deviation from the neutral equilibrium model for individual genes was interpreted within the context of intergene linkage disequilibrium and correlated patterns of functional differentiation. In contrast to the outcrosser Arabidopsis lyrata for which recombination is observed even within ATTI loci, our data suggest that response to selection was slowed in the inbreeding, annual A. thaliana because of interference among functionally divergent ATTI loci. PMID:15082560

  3. Human genes involved in copy number variation: mechanisms of origin, functional effects and implications for disease

    PubMed Central

    de Smith, A.J.; Walters, R.G.; Froguel, P.; Blakemore, A.I.

    2009-01-01

    Copy number variants (CNVs) overlap over 7000 genes, many of which are pivotal in biological pathways. The implications of this are profound, with consequences for evolutionary studies, population genetics, gene function and human phenotype, including elucidation of genetic susceptibility to major common diseases, the heritability of which has thus far defied full explanation. Even though this research is still in its infancy, CNVs have already been associated with a number of monogenic, syndromic and complex diseases: the development of high throughput and high resolution techniques for CNV screening is likely to bring further new insights into the contribution of copy number variation to common diseases. Amongst genes overlapped by CNVs, significant enrichments for certain gene ontology categories have been identified, including those related to immune responses and interactions with the environment. Genes in both of these categories are thought to be important in evolutionary adaptation and to be particular targets of natural selection. Thus, a full appreciation of copy number variation may be important for our understanding of human evolution. PMID:19287135

  4. Functional Polymorphisms in COX-2 Gene Are Correlated with the Risk of Oral Cancer

    PubMed Central

    Li, Dong; Hao, Shu-Hong; Sun, Yan; Hu, Chun-Mei; Ma, Zhi-Hua; Wang, Zhi Ming; Liu, Jie; Liu, Hong Bo; Ye, Ming; Zhang, Yu Fei; Yang, Dong Sheng; Shi, Guang

    2015-01-01

    Background. This meta-analysis investigated the association between functional COX-2 gene polymorphisms and the risk of oral cancer. Methods. Several electronic databases were searched for published studies using combinations of keywords related to COX-2 gene polymorphisms and oral cancer. After selection of relevant studies, following strict inclusion and exclusion criteria, data was performed using STATA 12.0 software. Results. We retrieved 83 studies from database search using specific search terms. After multiple rounds of selection and elimination, 7 studies were finally identified as suitable to be included in our present meta-analysis, based on their relevance and data integrity. These 7 studies contained a combined total of 2,296 oral cancer patients and 3,647 healthy controls. Our findings demonstrated that +837 T > C (rs5275) polymorphism in COX-2 showed statistically significant differences in gene frequencies in case and control groups in allele model and dominant model. Similar results were obtained with COX-2 gene polymorphism 765 G > C (rs20417). On the other hand, 1195 A > G (rs689466) polymorphism in COX-2 did not confer susceptibility to oral cancers. Conclusion. Based on our results, COX-2 gene polymorphisms, +837 T > C (rs5275) and ?765G > C (rs20417), showed clear links with oral cancer susceptibility, and the 1195A > G (rs689466) polymorphism did not show such a correlation. PMID:25977924

  5. Functional Analysis of Developmentally Regulated Genes chs7 and sec22 in the Ascomycete Sordaria macrospora.

    PubMed

    Traeger, Stefanie; Nowrousian, Minou

    2015-06-01

    During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. PMID:25873638

  6. Effective gene therapy in an authentic model of Tay-Sachs-related diseases.

    PubMed

    Cachón-González, M Begoña; Wang, Susan Z; Lynch, Andrew; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2006-07-01

    Tay-Sachs disease is a prototypic neurodegenerative disease. Lysosomal storage of GM2 ganglioside in Tay-Sachs and the related disorder, Sandhoff disease, is caused by deficiency of beta-hexosaminidase A, a heterodimeric protein. Tay-Sachs-related diseases (GM2 gangliosidoses) are incurable, but gene therapy has the potential for widespread correction of the underlying lysosomal defect by means of the secretion-recapture cellular pathway for enzymatic complementation. Sandhoff mice, lacking the beta-subunit of hexosaminidase, manifest many signs of classical human Tay-Sachs disease and, with an acute course, die before 20 weeks of age. We treated Sandhoff mice by stereotaxic intracranial inoculation of recombinant adeno-associated viral vectors encoding the complementing human beta-hexosaminidase alpha and beta subunit genes and elements, including an HIV tat sequence, to enhance protein expression and distribution. Animals survived for >1 year with sustained, widespread, and abundant enzyme delivery in the nervous system. Onset of the disease was delayed with preservation of motor function; inflammation and GM2 ganglioside storage in the brain and spinal cord was reduced. Gene delivery of beta-hexosaminidase A by using adeno-associated viral vectors has realistic potential for treating the human Tay-Sachs-related diseases. PMID:16801539

  7. Regulation and Function of Adult Neurogenesis: From Genes to Cognition

    PubMed Central

    Aimone, James B.; Li, Yan; Lee, Star W.; Clemenson, Gregory D.; Deng, Wei; Gage, Fred H.

    2014-01-01

    Adult neurogenesis in the hippocampus is a notable process due not only to its uniqueness and potential impact on cognition but also to its localized vertical integration of different scales of neuroscience, ranging from molecular and cellular biology to behavior. This review summarizes the recent research regarding the process of adult neurogenesis from these different perspectives, with particular emphasis on the differentiation and development of new neurons, the regulation of the process by extrinsic and intrinsic factors, and their ultimate function in the hippocampus circuit. Arising from a local neural stem cell population, new neurons progress through several stages of maturation, ultimately integrating into the adult dentate gyrus network. The increased appreciation of the full neurogenesis process, from genes and cells to behavior and cognition, makes neurogenesis both a unique case study for how scales in neuroscience can link together and suggests neurogenesis as a potential target for therapeutic intervention for a number of disorders. PMID:25287858

  8. HFE gene: Structure, function, mutations, and associated iron abnormalities.

    PubMed

    Barton, James C; Edwards, Corwin Q; Acton, Ronald T

    2015-12-15

    The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload. PMID:26456104

  9. Perilipin, a critical regulator of fat storage and breakdown, is a target gene of estrogen receptor-related receptor {alpha}

    SciTech Connect

    Akter, Mst. Hasina; Yamaguchi, Tomohiro; Hirose, Fumiko; Osumi, Takashi

    2008-04-11

    Perilipin is a protein localized on lipid droplet surfaces in adipocytes and steroidogenic cells, playing a central role in regulated lipolysis. Expression of the perilipin gene is markedly induced during adipogenesis. We found that transcription from the perilipin gene promoter is activated by an orphan nuclear receptor, estrogen receptor-related receptor (ERR){alpha}. A response element to this receptor was identified in the promoter region by a gene reporter assay, the electrophoretic-gel mobility-shift assay and the chromatin immunoprecipitation assay. Peroxisome proliferator-activated receptor {gamma} coactivator (PGC)-1{alpha} enhanced, whereas small heterodimer partner (SHP) repressed, the transactivating function of ERR{alpha} on the promoter. Thus, the perilipin gene expression is regulated by a transcriptional network controlling energy metabolism, substantiating the functional importance of perilipin in the maintenance of body energy balance.

  10. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    PubMed Central

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new therapeutics. This requires further in-depth knowledge of the similarities and differences between mouse and human RPE. Methods We performed a microarray study to identify and functionally annotate RPE specific gene expression in mouse and human RPE. We used a meticulous method to determine C57BL/6J mouse RPE signature genes, correcting for possible RNA contamination from its adjacent layers: the choroid and the photoreceptors. We compared the signature genes, gene expression profiles and functional annotations of the mouse and human RPE. Results We defined sets of mouse (64), human (171) and mouse–human interspecies (22) RPE signature genes. Not unexpectedly, our gene expression analysis and comparative functional annotation suggested that, in general, the mouse and human RPE are very similar. For example, we found similarities for general features, like “organ development” and “disorders related to neurological tissue”. However, detailed analysis of the molecular pathways and networks associated with RPE functions, suggested also multiple species-specific differences, some of which may be relevant for the development of AMD. For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE. Furthermore, functions assigned to mouse and human RPE expression profiles indicate (patho-) biological differences related to AMD, such as oxidative stress, Bruch’s membrane, immune-regulation and outer blood retina barrier. Conclusion These differences may be important for the development of new therapeutic strategies and translational studies in age-related macular degeneration. PMID:26517551

  11. Gene Expression during the Generation and Activation of Mouse Neutrophils: Implication of Novel Functional and Regulatory Pathways

    PubMed Central

    Ericson, Jeffrey A.; Duffau, Pierre; Yasuda, Kei; Ortiz-Lopez, Adriana; Rothamel, Katherine; Rifkin, Ian R.; Monach, Paul A.

    2014-01-01

    As part of the Immunological Genome Project (ImmGen), gene expression was determined in unstimulated (circulating) mouse neutrophils and three populations of neutrophils activated in vivo, with comparison among these populations and to other leukocytes. Activation conditions included serum-transfer arthritis (mediated by immune complexes), thioglycollate-induced peritonitis, and uric acid-induced peritonitis. Neutrophils expressed fewer genes than any other leukocyte population studied in ImmGen, and down-regulation of genes related to translation was particularly striking. However, genes with expression relatively specific to neutrophils were also identified, particularly three genes of unknown function: Stfa2l1, Mrgpr2a and Mrgpr2b. Comparison of genes up-regulated in activated neutrophils led to several novel findings: increased expression of genes related to synthesis and use of glutathione and of genes related to uptake and metabolism of modified lipoproteins, particularly in neutrophils elicited by thioglycollate; increased expression of genes for transcription factors in the Nr4a family, only in neutrophils elicited by serum-transfer arthritis; and increased expression of genes important in synthesis of prostaglandins and response to leukotrienes, particularly in neutrophils elicited by uric acid. Up-regulation of genes related to apoptosis, response to microbial products, NFkB family members and their regulators, and MHC class II expression was also seen, in agreement with previous studies. A regulatory model developed from the ImmGen data was used to infer regulatory genes involved in the changes in gene expression during neutrophil activation. Among 64, mostly novel, regulatory genes predicted to influence these changes in gene expression, Irf5 was shown to be important for optimal secretion of IL-10, IP-10, MIP-1?, MIP-1?, and TNF-? by mouse neutrophils in vitro after stimulation through TLR9. This data-set and its analysis using the ImmGen regulatory model provide a basis for additional hypothesis-based research on the importance of changes in gene expression in neutrophils in different conditions. PMID:25279834

  12. Differences in Human Cortical Gene Expression Match the Temporal Properties of Large-Scale Functional Networks

    PubMed Central

    Cioli, Claudia; Abdi, Hervé; Beaton, Derek; Burnod, Yves; Mesmoudi, Salma

    2014-01-01

    We explore the relationships between the cortex functional organization and genetic expression (as provided by the Allen Human Brain Atlas). Previous work suggests that functional cortical networks (resting state and task based) are organized as two large networks (differentiated by their preferred information processing mode) shaped like two rings. The first ring–Visual-Sensorimotor-Auditory (VSA)–comprises visual, auditory, somatosensory, and motor cortices that process real time world interactions. The second ring–Parieto-Temporo-Frontal (PTF)–comprises parietal, temporal, and frontal regions with networks dedicated to cognitive functions, emotions, biological needs, and internally driven rhythms. We found–with correspondence analysis–that the patterns of expression of the 938 genes most differentially expressed across the cortex organized the cortex into two sets of regions that match the two rings. We confirmed this result using discriminant correspondence analysis by showing that the genetic profiles of cortical regions can reliably predict to what ring these regions belong. We found that several of the proteins–coded by genes that most differentiate the rings–were involved in neuronal information processing such as ionic channels and neurotransmitter release. The systematic study of families of genes revealed specific proteins within families preferentially expressed in each ring. The results showed strong congruence between the preferential expression of subsets of genes, temporal properties of the proteins they code, and the preferred processing modes of the rings. Ionic channels and release-related proteins more expressed in the VSA ring favor temporal precision of fast evoked neural transmission (Sodium channels SCNA1, SCNB1 potassium channel KCNA1, calcium channel CACNA2D2, Synaptotagmin SYT2, Complexin CPLX1, Synaptobrevin VAMP1). Conversely, genes expressed in the PTF ring favor slower, sustained, or rhythmic activation (Sodium channels SCNA3, SCNB3, SCN9A potassium channels KCNF1, KCNG1) and facilitate spontaneous transmitter release (calcium channel CACNA1H, Synaptotagmins SYT5, Complexin CPLX3, and synaptobrevin VAMP2). PMID:25546015

  13. T-cell intracellular antigens function as tumor suppressor genes

    PubMed Central

    Sánchez-Jiménez, C; Ludeña, M D; Izquierdo, J M

    2015-01-01

    Knockdown of T-cell intracellular antigens TIA1 and TIAR in transformed cells triggers cell proliferation and tumor growth. Using a tetracycline-inducible system, we report here that an increased expression of TIA1 or TIAR in 293 cells results in reduced rates of cell proliferation. Ectopic expression of these proteins abolish endogenous TIA1 and TIAR levels via the regulation of splicing of their pre-mRNAs, and partially represses global translation in a phospho-eukaryotic initiation factor 2 alpha-dependent manner. This is accompanied by cell cycle arrest at G1/S and cell death through caspase-dependent apoptosis and autophagy. Genome-wide profiling illustrates a selective upregulation of p53 signaling pathway-related genes. Nude mice injected with doxycycline-inducible cells expressing TIA1 or TIAR retard, or even inhibit, growth of xenotumors. Remarkably, low expressions of TIA1 and TIAR correlate with poor prognosis in patients with lung squamous cell carcinoma. These findings strongly support the concept that TIA proteins act as tumor suppressor genes. PMID:25741594

  14. Cloning and Functional Characterization of Two BTB Genes in the Predatory Mite Metaseiulus occidentalis

    PubMed Central

    Wu, Ke; Hoy, Marjorie A.

    2015-01-01

    Proteins containing the BTB (Bric-à-brac, tramtrack, and Broad Complex) domain typically share low sequence similarities and are involved in a wide range of cellular functions. We previously identified two putative and closely related BTB genes, BTB1 and BTB2, in the genome of the predatory mite Metaseiulus occidentalis. In the current study, full-length BTB1 and BTB2 cDNAs were cloned and sequenced. BTB1 and BTB2 encode proteins of 380 and 401 amino acids, respectively. BTB1 and BTB2 proteins each contain an N-terminal BTB domain and no other identifiable domains. Thus, they belong to a large category of BTB-domain proteins that are widely distributed in eukaryotes, yet with largely unknown function(s). BTB1 and BTB2 gene knockdowns in M. occidentalis females using RNAi reduced their fecundity by approximately 40% and 73%, respectively, whereas knockdown had no impact on their survival or the development of their offspring. These findings suggest these two proteins may be involved in processes related to egg production in this predatory mite, expanding the list of functions attributed to these diverse proteins. PMID:26640898

  15. Study of the influence of genes related to muscle oxidative processes on beef color.

    PubMed

    Falomir-Lockhart, A H; Rogberg-Muñoz, A; Papaleo-Mazzucco, J; Goszczynski, D E; Lirón, J P; Fernández, M E; Añon, M C; Melucci, L M; Giovambattista, G

    2015-10-01

    The biochemical bases of meat color are determined by the concentration and redox state of myoglobin, hemoglobin, cytochromes, and other pigments. Post-mortem depletion of cellular oxygen results in oxidative stresses that consume NADH and affects reducing activity, while enzymatic detoxification influences the cellular oxidative processes, both affecting meat color. The aim of this work was to study the influence of several genes related to cellular oxidative processes that could affect CIELAB meat color parameters. The study was performed in steers that received a grass-based diet combined with grain, hays and silages. Results suggest a possible link between colorimetric parameters (a*, b* and chroma) and SNPs in the GSTP1 gene (P<0.05). Although the influence of the enzymes, encoded by GSTP1 gene, on meat color has been proposed previously at biochemical level and protein expression level, further association studies in different populations and functional studies of proteins are needed to confirm the genetic determination of that gene on meat color. PMID:26010991

  16. Cross-Species Comparison of Genes Related to Nutrient Sensing Mechanisms Expressed along the Intestine

    PubMed Central

    van der Wielen, Nikkie; van Avesaat, Mark; de Wit, Nicole J. W.; Vogels, Jack T. W. E.; Troost, Freddy; Masclee, Ad; Koopmans, Sietse-Jan; van der Meulen, Jan; Boekschoten, Mark V.; Müller, Michael; Hendriks, Henk F. J.; Witkamp, Renger F.; Meijerink, Jocelijn

    2014-01-01

    Introduction Intestinal chemosensory receptors and transporters are able to detect food-derived molecules and are involved in the modulation of gut hormone release. Gut hormones play an important role in the regulation of food intake and the control of gastrointestinal functioning. This mechanism is often referred to as “nutrient sensing”. Knowledge of the distribution of chemosensors along the intestinal tract is important to gain insight in nutrient detection and sensing, both pivotal processes for the regulation of food intake. However, most knowledge is derived from rodents, whereas studies in man and pig are limited, and cross-species comparisons are lacking. Aim To characterize and compare intestinal expression patterns of genes related to nutrient sensing in mice, pigs and humans. Methods Mucosal biopsy samples taken at six locations in human intestine (n?=?40) were analyzed by qPCR. Intestinal scrapings from 14 locations in pigs (n?=?6) and from 10 locations in mice (n?=?4) were analyzed by qPCR and microarray, respectively. The gene expression of glucagon, cholecystokinin, peptide YY, glucagon-like peptide-1 receptor, taste receptor T1R3, sodium/glucose cotransporter, peptide transporter-1, GPR120, taste receptor T1R1, GPR119 and GPR93 was investigated. Partial least squares (PLS) modeling was used to compare the intestinal expression pattern between the three species. Results and conclusion The studied genes were found to display specific expression patterns along the intestinal tract. PLS analysis showed a high similarity between human, pig and mouse in the expression of genes related to nutrient sensing in the distal ileum, and between human and pig in the colon. The gene expression pattern was most deviating between the species in the proximal intestine. Our results give new insights in interspecies similarities and provide new leads for translational research and models aiming to modulate food intake processes in man. PMID:25216051

  17. Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension

    PubMed Central

    Kotani, Kohei; Kawabe, Joji; Morikawa, Hiroyasu; Akahoshi, Tomohiko; Hashizume, Makoto; Shiomi, Susumu

    2015-01-01

    The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-?, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism. PMID:26549939

  18. Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

    SciTech Connect

    Ray, Anamika; Liu Jing; Ayoubi, Patricia; Pope, Carey

    2010-10-15

    Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NF{Kappa}B, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse/synaptic transmission and transcription/translation. Nine genes were differentially affected in all four CPF dosing groups. We conclude that the most robust, consistent changes in differential gene expression in neonatal forebrain across a range of acute CPF dosages occurred at an exposure level associated with the classical marker of OP toxicity, AChE inhibition. Disruption of multiple cellular pathways, in particular cell adhesion, may contribute to the developmental neurotoxicity potential of this pesticide.

  19. Caenorhabditis elegans has scores of hedgehog-related genes: sequence and expression analysis.

    PubMed

    Aspöck, G; Kagoshima, H; Niklaus, G; Bürglin, T R

    1999-10-01

    Previously, we have described novel families of genes, warthog (wrt) and groundhog (grd), in Caenorhabditis elegans. They are related to Hedgehog (Hh) through the carboxy-terminal autoprocessing domain (called Hog or Hint). A comprehensive survey revealed 10 genes with Hog/Hint modules in C. elegans. Five of these are associated with a Wart domain in wrt genes, and three with multiple copies of the Ground domain in grd genes. Both the Wart domain and the Ground domain occur also in genes encoding no Hog domain. Further, we define a new group of genes related to the grd genes, called ground-like (grl). Overall, C. elegans has more than 50 genes belonging to these gene families. Phylogenetic and sequence analysis shows that the wrt, grd, and grl genes are derived from each other. Further examination reveals a sequence motif with similarity to the core of the amino-terminal-signaling domain of Hh proteins. Our data suggest that the wrt, grd, grl, and hh genes are derived from a single ancestral gene. wrt, grd, and grl genes are also present in other nematodes, but so far not in any other phyla. Conversely, hh is not found presently in C. elegans nor other nematodes. Thus, the nematode genes could be the homologs of Hh molecules in other phyla. The membrane molecule Patched has been shown previously to be a receptor of Hh. Many Patched-related proteins are present in C. elegans, which may be targets of the hh-related genes. No Hedgehog-interacting protein (Hip) was found. We analyzed the expression patterns of eight wrt and eight grd genes. The results show that some closely related genes are expressed in the same tissues, but, overall, the expression patterns are diverse, comprising hypodermis, seam cells, the excretory cell, sheath and socket cells, and different types of neurons. PMID:10523520

  20. Functional analysis of human cancer-associated genes and their association with the testes and epididymis

    PubMed Central

    HUA, XIU-FENG; WANG, XUE-BO; LIU, FU-JUN

    2013-01-01

    Human cancer-associated UniGene sets (NCBI GeneBank) provide a platform for identifying differentially-expressed genes in human cancers. The present study identified and characterized a set of human cancer-associated genes using the Digital Differential Display (DDD) and functional analysis tools. A total of 1,904 genes were differentially expressed in 15 cancer types, including genes that had been previously shown to be specific in certain human cancers. A total of 274 genes were uniquely expressed in certain cancer types, including 37 genes that were highly expressed in the human testes and epididymis. These genes mainly functioned as ribosomal proteins, enzymes, receptors, secretory proteins and cell adhesion molecules. The most common domains that were encoded by the cancer-associated genes were those of cytochrome P450 CYP2D6, serpin and apolipoprotein A-I. A further gene ontology (GO) enrichment analysis revealed seven major functional clusters, which corresponded to the enriched pathways involved in cancer. The present study provides a source of cancer-associated genes and their functions. The results provide new insights into cancer biology and the involvement of highly-expressed epididymal genes in cancer biomarkers. PMID:24137416

  1. Analyses of soil microbial community compositions and functional genes reveal potential consequences of natural forest succession

    PubMed Central

    Cong, Jing; Yang, Yunfeng; Liu, Xueduan; Lu, Hui; Liu, Xiao; Zhou, Jizhong; Li, Diqiang; Yin, Huaqun; Ding, Junjun; Zhang, Yuguang

    2015-01-01

    The succession of microbial community structure and function is a central ecological topic, as microbes drive the Earth’s biogeochemical cycles. To elucidate the response and mechanistic underpinnings of soil microbial community structure and metabolic potential relevant to natural forest succession, we compared soil microbial communities from three adjacent natural forests: a coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf forest (DBF) on Shennongjia Mountain in central China. In contrary to plant communities, the microbial taxonomic diversity of the DBF was significantly (P?functional diversity was also highest in the DBF. Furthermore, a network analysis of microbial carbon and nitrogen cycling genes showed the network for the DBF samples was relatively large and tight, revealing strong couplings between microbes. Soil temperature, reflective of climate regimes, was important in shaping microbial communities at both taxonomic and functional gene levels. As a first glimpse of both the taxonomic and functional compositions of soil microbial communities, our results suggest that microbial community structure and function potentials will be altered by future environmental changes, which have implications for forest succession. PMID:25943705

  2. Analyses of soil microbial community compositions and functional genes reveal potential consequences of natural forest succession

    NASA Astrophysics Data System (ADS)

    Cong, Jing; Yang, Yunfeng; Liu, Xueduan; Lu, Hui; Liu, Xiao; Zhou, Jizhong; Li, Diqiang; Yin, Huaqun; Ding, Junjun; Zhang, Yuguang

    2015-05-01

    The succession of microbial community structure and function is a central ecological topic, as microbes drive the Earth’s biogeochemical cycles. To elucidate the response and mechanistic underpinnings of soil microbial community structure and metabolic potential relevant to natural forest succession, we compared soil microbial communities from three adjacent natural forests: a coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf forest (DBF) on Shennongjia Mountain in central China. In contrary to plant communities, the microbial taxonomic diversity of the DBF was significantly (P?functional diversity was also highest in the DBF. Furthermore, a network analysis of microbial carbon and nitrogen cycling genes showed the network for the DBF samples was relatively large and tight, revealing strong couplings between microbes. Soil temperature, reflective of climate regimes, was important in shaping microbial communities at both taxonomic and functional gene levels. As a first glimpse of both the taxonomic and functional compositions of soil microbial communities, our results suggest that microbial community structure and function potentials will be altered by future environmental changes, which have implications for forest succession.

  3. Analyses of soil microbial community compositions and functional genes reveal potential consequences of natural forest succession.

    PubMed

    Cong, Jing; Yang, Yunfeng; Liu, Xueduan; Lu, Hui; Liu, Xiao; Zhou, Jizhong; Li, Diqiang; Yin, Huaqun; Ding, Junjun; Zhang, Yuguang

    2015-01-01

    The succession of microbial community structure and function is a central ecological topic, as microbes drive the Earth's biogeochemical cycles. To elucidate the response and mechanistic underpinnings of soil microbial community structure and metabolic potential relevant to natural forest succession, we compared soil microbial communities from three adjacent natural forests: a coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf forest (DBF) on Shennongjia Mountain in central China. In contrary to plant communities, the microbial taxonomic diversity of the DBF was significantly (P?functional diversity was also highest in the DBF. Furthermore, a network analysis of microbial carbon and nitrogen cycling genes showed the network for the DBF samples was relatively large and tight, revealing strong couplings between microbes. Soil temperature, reflective of climate regimes, was important in shaping microbial communities at both taxonomic and functional gene levels. As a first glimpse of both the taxonomic and functional compositions of soil microbial communities, our results suggest that microbial community structure and function potentials will be altered by future environmental changes, which have implications for forest succession. PMID:25943705

  4. Eukaryotic Evolutionary Transitions Are Associated with Extreme Codon Bias in Functionally-Related Proteins

    PubMed Central

    Hudson, Nicholas J.; Gu, Quan; Nagaraj, Shivashankar H.; Ding, Yong-Sheng; Dalrymple, Brian P.; Reverter, Antonio

    2011-01-01

    Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins – perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair – a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function – which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins – perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor – which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation. PMID:21966531

  5. Alterations of tumor-related genes do not exactly match the histopathological grade in gastric adenocarcinomas

    PubMed Central

    Liu, Guo-Yan; Liu, Kun-Hong; Zhang, Yong; Wang, Yu-Zhi; Wu, Xiao-Hong; Lu, Yi-Zhuo; Pan, Chao; Yin, Ping; Liao, Hong-Feng; Su, Ji-Qin; Ge, Qing; Luo, Qi; Xiong, Bin

    2010-01-01

    AIM: To investigate the diverse characteristics of different pathological gradings of gastric adenocarcinoma (GA) using tumor-related genes. METHODS: GA tissues in different pathological gradings and normal tissues were subjected to tissue arrays. Expressions of 15 major tumor-related genes were detected by RNA in situ hybridization along with 3’ terminal digoxin-labeled anti-sense single stranded oligonucleotide and locked nucleic acid modifying probe within the tissue array. The data obtained were processed by support vector machines by four different feature selection methods to discover the respective critical gene/gene subsets contributing to the GA activities of different pathological gradings. RESULTS: In comparison of poorly differentiated GA with normal tissues, tumor-related gene TP53 plays a key role, although other six tumor-related genes could also achieve the Area Under Curve (AUC) of the receiver operating characteristic independently by more than 80%. Comparing the well differentiated GA with normal tissues, we found that 11 tumor-related genes could independently obtain the AUC by more than 80%, but only the gene subsets, TP53, RB and PTEN, play a key role. Only the gene subsets, Bcl10, UVRAG, APC, Beclin1, NM23, PTEN and RB could distinguish between the poorly differentiated and well differentiated GA. None of a single gene could obtain a valid distinction. CONCLUSION: Different from the traditional point of view, the well differentiated cancer tissues have more alterations of important tumor-related genes than the poorly differentiated cancer tissues. PMID:20205286

  6. Cell wall-related proteins of unknown function: missing links in plant cell wall development.

    PubMed

    Mewalal, Ritesh; Mizrachi, Eshchar; Mansfield, Shawn D; Myburg, Alexander A

    2014-06-01

    Lignocellulosic biomass is an important feedstock for the pulp and paper industry as well as emerging biofuel and biomaterial industries. However, the recalcitrance of the secondary cell wall to chemical or enzymatic degradation remains a major hurdle for efficient extraction of economically important biopolymers such as cellulose. It has been estimated that approximately 10-15% of about 27,000 protein-coding genes in the Arabidopsis genome are dedicated to cell wall development; however, only about 130 Arabidopsis genes thus far have experimental evidence validating cell wall function. While many genes have been implicated through co-expression analysis with known genes, a large number are broadly classified as proteins of unknown function (PUFs). Recently the functionality of some of these unknown proteins in cell wall development has been revealed using reverse genetic approaches. Given the large number of cell wall-related PUFs, how do we approach and subsequently prioritize the investigation of such unknown genes that may be essential to or influence plant cell wall development and structure? Here, we address the aforementioned question in two parts; we first identify the different kinds of PUFs based on known and predicted features such as protein domains. Knowledge of inherent features of PUFs may allow for functional inference and a concomitant link to biological context. Secondly, we discuss omics-based technologies and approaches that are helping identify and prioritize cell wall-related PUFs by functional association. In this way, hypothesis-driven experiments can be designed for functional elucidation of many proteins that remain missing links in our understanding of plant cell wall biosynthesis. PMID:24683037

  7. Parallel sites implicate functional convergence of the hearing gene prestin among echolocating mammals.

    PubMed

    Liu, Zhen; Qi, Fei-Yan; Zhou, Xin; Ren, Hai-Qing; Shi, Peng

    2014-09-01

    Echolocation is a sensory system whereby certain mammals navigate and forage using sound waves, usually in environments where visibility is limited. Curiously, echolocation has evolved independently in bats and whales, which occupy entirely different environments. Based on this phenotypic convergence, recent studies identified several echolocation-related genes with parallel sites at the protein sequence level among different echolocating mammals, and among these, prestin seems the most promising. Although previous studies analyzed the evolutionary mechanism of prestin, the functional roles of the parallel sites in the evolution of mammalian echolocation are not clear. By functional assays, we show that a key parameter of prestin function, 1/?, is increased in all echolocating mammals and that the N7T parallel substitution accounted for this functional convergence. Moreover, another parameter, V1/2, was shifted toward the depolarization direction in a toothed whale, the bottlenose dolphin (Tursiops truncatus) and a constant-frequency (CF) bat, the Stoliczka's trident bat (Aselliscus stoliczkanus). The parallel site of I384T between toothed whales and CF bats was responsible for this functional convergence. Furthermore, the two parameters (1/? and V1/2) were correlated with mammalian high-frequency hearing, suggesting that the convergent changes of the prestin function in echolocating mammals may play important roles in mammalian echolocation. To our knowledge, these findings present the functional patterns of echolocation-related genes in echolocating mammals for the first time and rigorously demonstrate adaptive parallel evolution at the protein sequence level, paving the way to insights into the molecular mechanism underlying mammalian echolocation. PMID:24951728

  8. The Xenopus doublesex-related gene Dmrt5 is required for olfactory placode neurogenesis.

    PubMed

    Parlier, Damien; Moers, Virginie; Van Campenhout, Claude; Preillon, Julie; Leclère, Lucas; Saulnier, Amandine; Sirakov, Maria; Busengdal, Henriette; Kricha, Sadia; Marine, Jean-Christophe; Rentzsch, Fabian; Bellefroid, Eric J

    2013-01-01

    The Dmrt (doublesex and mab-3 related transcription factor) genes encode a large family of evolutionarily conserved transcription factors whose function in sex specific differentiation has been well studied in all animal lineages. In vertebrates, their function is not restricted to the developing gonads. For example, Xenopus Dmrt4 is essential for neurogenesis in the olfactory system. Here we have isolated and characterized Xenopus Dmrt5 and found that it is coexpressed with Dmrt4 in the developing olfactory placodes. As Dmrt4, Dmrt5 is positively regulated in the ectoderm by neural inducers and negatively by proneural factors. Both Dmrt5 and Dmrt4 genes are also activated by the combined action of the transcription factor Otx2, broadly transcribed in the head ectoderm and of Notch signaling, activated in the anterior neural ridge. As for Dmrt4, knockdown of Dmrt5 impairs neurogenesis in the embryonic olfactory system and in neuralized animal caps. Conversely, its overexpression promotes neuronal differentiation in animal caps, a property that requires the conserved C-terminal DMA and DMB domains. We also found that the sea anenome Dmrt4/5 related gene NvDmrtb also induces neurogenesis in Xenopus animal caps and that conversely, its knockdown in Nematostella reduces elav-1 positive neurons. Together, our data identify Dmrt5 as a novel important regulator of neurogenesis whose function overlaps with that of Dmrt4 during Xenopus olfactory system development. They also suggest that Dmrt may have had a role in neurogenesis in the last common ancestor of cnidarians and bilaterians. PMID:23064029

  9. Salt resistance genes revealed by functional metagenomics from brines and moderate-salinity rhizosphere within a hypersaline environment

    PubMed Central

    Mirete, Salvador; Mora-Ruiz, Merit R.; Lamprecht-Grandío, María; de Figueras, Carolina G.; Rosselló-Móra, Ramon; González-Pastor, José E.

    2015-01-01

    Hypersaline environments are considered one of the most extreme habitats on earth and microorganisms have developed diverse molecular mechanisms of adaptation to withstand these conditions. The present study was aimed at identifying novel genes from the microbial communities of a moderate-salinity rhizosphere and brine from the Es Trenc saltern (Mallorca, Spain), which could confer increased salt resistance to Escherichia coli. The microbial diversity assessed by pyrosequencing of 16S rRNA gene libraries revealed the presence of communities that are typical in such environments and the remarkable presence of three bacterial groups never revealed as major components of salt brines. Metagenomic libraries from brine and rhizosphere samples, were transferred to the osmosensitive strain E. coli MKH13, and screened for salt resistance. Eleven genes that conferred salt resistance were identified, some encoding for well-known proteins previously related to osmoadaptation such as a glycerol transporter and a proton pump, whereas others encoded proteins not previously related to this function in microorganisms such as DNA/RNA helicases, an endonuclease III (Nth) and hypothetical proteins of unknown function. Furthermore, four of the retrieved genes were cloned and expressed in Bacillus subtilis and they also conferred salt resistance to this bacterium, broadening the spectrum of bacterial species in which these genes can function. This is the first report of salt resistance genes recovered from metagenomes of a hypersaline environment. PMID:26528268

  10. Evolutionary history of the Rh blood group-related genes in vertebrates.

    PubMed

    Kitano, T; Saitou, N

    2000-08-01

    Rh and its homologous Rh50 gene products are considered to form heterotetramers on erythrocyte membranes. Rh protein has Rh blood group antigen sites, while Rh50 protein does not, and is more conserved than Rh protein. We previously determined both Rh and Rh50 gene cDNA coding regions from mouse and rat, and carried out phylogenetic analyses. In this study, we determined Rh50 gene cDNA coding regions from African clawed frog and Japanese medaka fish, and examined the long-term evolution of the Rh blood group and related genes. We constructed the phylogenetic tree from amino acid sequences. Rh50 genes of African clawed frog and Japanese medaka fish formed a cluster with mammalian Rh50 genes. The gene duplication time between Rh and Rh50 genes was estimated to be about 510 million years ago based on this tree. This period roughly corresponds to the Cambrian, before the divergence between jawless fish and jawed vertebrates. We also BLAST-searched an amino acid sequence database, and the Rh blood group and related genes were found to have homology with ammonium transporter genes of many organisms. Ammonium transporter genes can be classified into two major groups (amt alpha and amt beta). Both groups contain genes from three domains (bacteria, archaea, and eukaryota). The Rh blood group and related genes are separated from both amt alpha and beta groups. PMID:10970100

  11. Improvement-related functional plasticity following pitch memory training

    E-print Network

    Gaser, Christian

    Improvement-related functional plasticity following pitch memory training Nadine Gaab,a Christian to the functional changes that were shown. In contrast, motor training studies (Jenkins et al., 1994; Schlaug et al; revised 20 October 2005; accepted 18 November 2005 Available online 19 January 2006 Functional activation

  12. Evolution and Functional Classification of Vertebrate Gene Deserts

    SciTech Connect

    Ovcharenko, I; Loots, G; Nobrega, M; Hardison, R; Miller, W; Stubbs, L

    2004-07-14

    Gene deserts, long stretches of DNA sequence devoid of protein coding genes, span approximately one quarter of the human genome. Through human-chicken genome comparisons we were able to characterized one third of human gene deserts as evolutionarily stable - they are highly conserved in vertebrates, resist chromosomal rearrangements, and contain multiple conserved non-coding elements physically linked to their neighboring genes. A linear relationship was observed between human and chicken orthologous stable gene deserts, where the human deserts appear to have expanded homogeneously by a uniform accumulation of repetitive elements. Stable gene deserts are associated with key vertebrate genes that construct the framework of vertebrate development; many of which encode transcription factors. We show that the regulatory machinery governing genes associated with stable gene deserts operates differently from other regions in the human genome and relies heavily on distant regulatory elements. The regulation guided by these elements is independent of the distance between the gene and its distant regulatory element, or the distance between two distant regulatory cassettes. The location of gene deserts and their associated genes in the genome is independent of chromosomal length or content presenting these regions as well-bounded regions evolving separately from the rest of the genome.

  13. Polyphenol Oxidase Gene Structure in Wheat and Related Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since PPO is known to be the major cause of browning reactions that discolour Asian noodles and other wheat products, a better understanding of PPO gene structure should contribute to minimizing the deleterious effects of PPO via wheat breeding and improvement. A PPO gene model has emerged that iden...

  14. Advanced Functional Materials for Energy Related Applications

    NASA Astrophysics Data System (ADS)

    Sasan, Koroush

    The current global heavy dependency on fossil fuels gives rise to two critical problems: I) fossil fuels will be depleted in the near future; II) the release of green house gas CO2 generated by the combustion of fossil fuels contributes to global warming. To potentially address both problems, this dissertation documents three primary areas of investigation related to the development of alternative energy sources: electrocatalysts for fuel cells, photocatalysts for hydrogen generation, and photoreduction catalysts for converting CO2 to CH4. Fuel cells could be a promising source of alternative energy. Decreasing the cost and improving the durability and power density of Pt/C as a catalyst for reducing oxygen are major challenges for developing fuel cells. To address these concerns, we have synthesized a Nitrogen-Sulfur-Iron-doped porous carbon material. Our results indicate that the synthesized catalyst exhibits not only higher current density and stability but also higher tolerance to crossover chemicals than the commercial Pt/C catalyst. More importantly, the synthetic method is simple and inexpensive. Using photocatalysts and solar energy is another potential alternative solution for energy demand. We have synthesized a new biomimetic heterogeneous photocatalyst through the incorporation of homogeneous complex 1 [(i-SCH 2)2NC(O)C5H4N]-Fe2(CO) 6] into the highly robust zirconium-porphyrin based metal-organic framework (ZrPF). As photosensitizer ZrPF absorbs the visible light and produces photoexcited electrons that can be transferred through axial covalent bond to di-nuclear complex 1 for hydrogen generation. Additionally, we have studied the photoreduction of CO2 to CH4 using self-doped TiO2 (Ti+3@TiO 2) as photocatalytic materials. The incorporation of Ti3+ into TiO2 structures narrows the band gap, leading to significantly increased photocatalytic activity for the reduction of CO2 into renewable hydrocarbon fuel in the presence of water vapor under visible light. Finally, we demonstrate that open-framework chalcogenides can also be used as efficient photocatalysts for the reduction of CO2 to CH 4. These materials contain covalent superlattices of nanosized supertetrahedral clusters, which can be made with different metal cations to provide high electrical conductivity and current density as well as materials with different band gaps. The ability in incorporating different metal cations further enhances the material's photocatalytic activity, which could possibly provide alternative technologies for reducing CO2 in the atmosphere and simultaneously producing fuel.

  15. Epigenomics and Aging How epigenetic regulation of gene expression is related to getting older

    E-print Network

    Brutlag, Doug

    other than changes in DNA sequence. Affects which genes are transcribed. Reason for cellEpigenomics and Aging How epigenetic regulation of gene expression is related to getting older #12;What is epigenomics? Study of heritable changes in phenotype or gene expression caused by mechanisms

  16. 0-7803-9387-2/05/$20.00 2005 IEEE Predicting Single Genes Related to

    E-print Network

    Zell, Andreas

    0-7803-9387-2/05/$20.00 ©2005 IEEE Predicting Single Genes Related to Immune-Relevant Processes C¨ubingen, 72074 T¨ubingen, Germany Abstract-- In this paper we address the problem of predicting gene activities by finding gene regulatory dependencies in exper- imental DNA microarray data. Only few approaches to infer

  17. Mapping Medline Papers, Genes, and Proteins Related to Melanoma Research Kevin W. Boyack

    E-print Network

    Börner, Katy

    Characterization The process of generating a map that shows the association linkages between papers, genesMapping Medline Papers, Genes, and Proteins Related to Melanoma Research Kevin W. Boyack , Ketan years? Which parts of this research field are correlated with the study of genes and proteins

  18. Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments

    PubMed Central

    Akkiprik, Mustafa; Peker, ?rem; Özmen, Tolga; Güllü Amuran, Gökçe; Güllüo?lu, Bahad?r M.; Kaya, Handan; Özer, Ay?e

    2015-01-01

    IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer. PMID:26569312

  19. Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments.

    PubMed

    Akkiprik, Mustafa; Peker, ?rem; Özmen, Tolga; Amuran, Gökçe Güllü; Güllüo?lu, Bahad?r M; Kaya, Handan; Özer, Ay?e

    2015-01-01

    IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer. PMID:26569312

  20. Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo.

    PubMed

    Du, Guizhen; Hu, Jialei; Huang, Hongyu; Qin, Yufeng; Han, Xiumei; Wu, Di; Song, Ling; Xia, Yankai; Wang, Xinru

    2013-02-01

    Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500?µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo. PMID:23074026

  1. RNA-Seq analysis of yak ovary: improving yak gene structure information and mining reproduction-related genes.

    PubMed

    Lan, DaoLiang; Xiong, XianRong; Wei, YanLi; Xu, Tong; Zhong, JinCheng; Zhi, XiangDong; Wang, Yong; Li, Jian

    2014-09-01

    RNA-Seq, a high-throughput (HT) sequencing technique, has been used effectively in large-scale transcriptomic studies, and is particularly useful for improving gene structure information and mining of new genes. In this study, RNA-Seq HT technology was employed to analyze the transcriptome of yak ovary. After Illumina-Solexa deep sequencing, 26826516 clean reads with a total of 4828772880 bp were obtained from the ovary library. Alignment analysis showed that 16992 yak genes mapped to the yak genome and 3734 of these genes were involved in alternative splicing. Gene structure refinement analysis showed that 7340 genes that were annotated in the yak genome could be extended at the 5' or 3' ends based on the alignments been the transcripts and the genome sequence. Novel transcript prediction analysis identified 6321 new transcripts with lengths ranging from 180 to 14884 bp, and 2267 of them were predicted to code proteins. BLAST analysis of the new transcripts showed that 1200?4933 mapped to the non-redundant (nr), nucleotide (nt) and/or SwissProt sequence databases. Comparative statistical analysis of the new mapped transcripts showed that the majority of them were similar to genes in Bos taurus (41.4%), Bos grunniens mutus (33.0%), Ovis aries (6.3%), Homo sapiens (2.8%), Mus musculus (1.6%) and other species. Functional analysis showed that these expressed genes were involved in various Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes pathways. GO analysis of the new transcripts found that the largest proportion of them was associated with reproduction. The results of this study will provide a basis for describing the normal transcriptome map of yak ovary and for future studies on yak breeding performance. Moreover, the results confirmed that RNA-Seq HT technology is highly advantageous in improving gene structure information and mining of new genes, as well as in providing valuable data to expand the yak genome information. PMID:24907937

  2. Functionalized nanoparticles for AMF-induced gene and drug delivery

    NASA Astrophysics Data System (ADS)

    Biswas, Souvik

    The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the non-toxic magnetoplexes (magnetic nanoparticle + pDNA complex) derived from dMLP deliver pDNA into mammalian cells even without external magnetic assistance. To date, dMLP is the only polymer-free magnetic gene delivery system that can deliver pDNA without any magnetic assistance. Chapter 3 of this thesis outlines the synthesis and characterization of other oxime ether lipids and details studies using derived-lipoplexes. These lipids were evaluated in pDNA and siRNA transfection studies in various mammalian cell lines. This work constitutes the first use of an oxime ether as the linking domain in cationic transfection lipids. These biocompatible oxime ether lipids can be readily assembled by click chemistry through ligation of hydrophobic aldehydes with quaternary ammonium aminooxy salts. Our studies showed that the oxime ether lipids transfected pDNA and siRNA efficiently in MCF-7, H 1792, and in PAR C10 cells comparable to and in some cases better than commercial transfection lipids. Chapter 4 describes the design and characterization of a nano-magnetic delivery system for AMF-induced drug (doxorubicin) release. In efforts to develop a magnetic formulation free from thermosensitive materials, such as hydrogels, we synthesized three nanoparticle-based doxorubicin formulations using charge interactions as the key associative force. To do so, we synthesized and characterized a novel cationic oxime ether conjugate at C-13 of doxorubicin. Our investigation indicated that the positive charge of the oxime ether drug conjugate tended to bind better to the negatively charged nanoparticle than did the other formulations prepared in stepwise manner. Our findings show that the nano-magnetic formulations remained essestially inactive at body temperature (37.5 °C) and released a majority of the cargo only when exposed to an external AMF. Our designed magnetic drug delivery platform is the first example of an AMF-inducible system that does not depend on the inclusion of thermosensitive materials. Finally, we have developed a bioanalytical application of the highly chemosele

  3. Textual Information for Predicting Functional Properties of the Genes Oana Frunza and Diana Inkpen

    E-print Network

    Inkpen, Diana

    defini- tion consists of those genes labeled with either the "change" or the "control" labelTextual Information for Predicting Functional Properties of the Genes Oana Frunza and Diana Inkpen activity when single genes are knocked out. Experiments with results are presented when models are trained

  4. Comparative RNAi Screens in C. elegans and C. briggsae Reveal the Impact of Developmental System Drift on Gene Function

    PubMed Central

    Verster, Adrian J.; Ramani, Arun K.; McKay, Sheldon J.; Fraser, Andrew G.

    2014-01-01

    Although two related species may have extremely similar phenotypes, the genetic networks underpinning this conserved biology may have diverged substantially since they last shared a common ancestor. This is termed Developmental System Drift (DSD) and reflects the plasticity of genetic networks. One consequence of DSD is that some orthologous genes will have evolved different in vivo functions in two such phenotypically similar, related species and will therefore have different loss of function phenotypes. Here we report an RNAi screen in C. elegans and C. briggsae to identify such cases. We screened 1333 genes in both species and identified 91 orthologues that have different RNAi phenotypes. Intriguingly, we find that recently evolved genes of unknown function have the fastest evolving in vivo functions and, in several cases, we identify the molecular events driving these changes. We thus find that DSD has a major impact on the evolution of gene function and we anticipate that the C. briggsae RNAi library reported here will drive future studies on comparative functional genomics screens in these nematodes. PMID:24516395

  5. Connectivity of vertebrate genomes: Paired-related homeobox (Prrx) genes in spotted gar, basal teleosts, and tetrapods?

    PubMed Central

    Braasch, Ingo; Guiguen, Yann; Loker, Ryan; Letaw, John H.; Ferrara, Allyse; Bobe, Julien; Postlethwait, John H.

    2014-01-01

    Teleost fish are important models for human biology, health, and disease. Because genome duplication in a teleost ancestor (TGD) impacts the evolution of teleost genome structure and gene repertoires, we must discriminate gene functions that are shared and ancestral from those that are lineage-specific in teleosts or tetrapods to accurately apply inferences from teleost disease models to human health. Generalizations must account both for the TGD and for divergent evolution between teleosts and tetrapods after the likely two rounds of genome duplication shared by all vertebrates. Progress in sequencing techniques provides new opportunities to generate genomic and transcriptomic information from a broad range of phylogenetically informative taxa that facilitate detailed understanding of gene family and gene function evolution. We illustrate here the use of new sequence resources from spotted gar (Lepisosteus oculatus), a rayfin fish that diverged from teleosts before the TGD, as well as RNA-Seq data from gar and multiple teleost lineages to reconstruct the evolution of the Paired-related homeobox (Prrx) transcription factor gene family, which is involved in the development of mesoderm and neural crest-derived mesenchyme. We show that for Prrx genes, the spotted gar genome and gene expression patterns mimic mammals better than teleosts do. Analyses force the seemingly paradoxical conclusion that regulatory mechanisms for the limb expression domains of Prrx genes existed before the evolution of paired appendages. Detailed evolutionary analyses like those reported here are required to identify fish species most similar to the human genome to optimally connect fish models to human gene functions in health and disease. PMID:24486528

  6. Connectivity of vertebrate genomes: Paired-related homeobox (Prrx) genes in spotted gar, basal teleosts, and tetrapods.

    PubMed

    Braasch, Ingo; Guiguen, Yann; Loker, Ryan; Letaw, John H; Ferrara, Allyse; Bobe, Julien; Postlethwait, John H

    2014-06-01

    Teleost fish are important models for human biology, health, and disease. Because genome duplication in a teleost ancestor (TGD) impacts the evolution of teleost genome structure and gene repertoires, we must discriminate gene functions that are shared and ancestral from those that are lineage-specific in teleosts or tetrapods to accurately apply inferences from teleost disease models to human health. Generalizations must account both for the TGD and for divergent evolution between teleosts and tetrapods after the likely two rounds of genome duplication shared by all vertebrates. Progress in sequencing techniques provides new opportunities to generate genomic and transcriptomic information from a broad range of phylogenetically informative taxa that facilitate detailed understanding of gene family and gene function evolution. We illustrate here the use of new sequence resources from spotted gar (Lepisosteus oculatus), a rayfin fish that diverged from teleosts before the TGD, as well as RNA-Seq data from gar and multiple teleost lineages to reconstruct the evolution of the Paired-related homeobox (Prrx) transcription factor gene family, which is involved in the development of mesoderm and neural crest-derived mesenchyme. We show that for Prrx genes, the spotted gar genome and gene expression patterns mimic mammals better than teleosts do. Analyses force the seemingly paradoxical conclusion that regulatory mechanisms for the limb expression domains of Prrx genes existed before the evolution of paired appendages. Detailed evolutionary analyses like those reported here are required to identify fish species most similar to the human genome to optimally connect fish models to human gene functions in health and disease. PMID:24486528

  7. Spatial patterns of denitrification and its functional genes in peatlands

    NASA Astrophysics Data System (ADS)

    Mander, Ülo; Ligi, Teele; Truu, Marika; Truu, Jaak; Pärn, Jaan; Egorov, Sergey; Järveoja, Järvi; Vohla, Christina; Maddison, Martin; Soosaar, Kaido; Oopkaup, Kristjan; Teemusk, Alar; Preem, Jens-Konrad; Uuemaa, Evelyn

    2014-05-01

    This study is aimed to analyse relationships between the environmental factors and the spatial distribution of the main functional genes nirS, nirK, and nosZ regulating the denitrification process. Variations in hydrological regime, soil temperature and peat quality have been taken into the consideration at both local and global scale. Measurements of greenhouse gas (GHG) emissions using static chambers, groundwater analysis, gas and peat sampling for further laboratory analysis has been conducted in various peatlands in Iceland (two study areas, 2011), Transylvania/Romania (2012), Santa Catarina/Brazil (2012), Quebec/Canada (2012), Bashkortostan/Russian Federation (two study areas, 2012), Sichuan/China (2012), Estonia (two study areas, 2012), Florida/USA (2013, Sologne/France (2013), Jugra in West Siberia/Russia (2013), Uganda (2013), French Guyana (two study areas, 2013), Tasmania (two study areas, 2014) and New Zealand (two study areas, 2014). In each study area at least 2 transects along the groundwater depth gradient, one preferably in undisturbed, another one in drained area, and at least 3 rows of sampling sites (3-5 replicate chambers and 1 piezometer and soil sampling plot in each) in both has been established for studies. In each transect GHG emission was measured during 2-3 days in at least 5 sessions. In addition, organic sediments from the artificial riverine wetlands in Ohio/USA in 2009 and relevant gas emission studies have been used in the analyses. In the laboratories of Estonian University of Life Sciences and the University of Tartu, the peat chemical quality (pH, N, P, C, NH4, NO3) and N2O, CO2, and CH4 concentration in gas samples (50mL glass bottles and exetainers) were analysed. The peat samples for further pyrosequencing and qPCR analyses are stored in fridge by -22oC. This presentation will consider the variation of GHG emissions and hydrological conditions in the study sites. In addition, several selected biophysical factors will be taken into account. Further study will include peatland sites in Montana/USA, Columbia (Andes), Tierra del Fuego/Argentina, Pyrenees/Spain, Savo/Finland, the Netherlands, Okawango/Botswana, Heilongjiang/China, and Kamchatka/Russian Federation. Also, additional analysis will be conducted on the relationships between the intensity of CH4 emissions and methanogenesis regulating functional genes mcrA, pmoA, and dsrAB.

  8. Functional Gene Polymorphism to Reveal Species History: The Case of the CRTISO Gene in Cultivated Carrots

    PubMed Central

    Clotault, Jérémy; Huet, Sébastien; Briard, Mathilde; Peltier, Didier; Geoffriau, Emmanuel

    2013-01-01

    Background Carrot is a vegetable cultivated worldwide for the consumption of its root. Historical data indicate that root colour has been differentially selected over time and according to geographical areas. Root pigmentation depends on the relative proportion of different carotenoids for the white, yellow, orange and red types but only internally for the purple one. The genetic control for root carotenoid content might be partially associated with carotenoid biosynthetic genes. Carotenoid isomerase (CRTISO) has emerged as a regulatory step in the carotenoid biosynthesis pathway and could be a good candidate to show how a metabolic pathway gene reflects a species genetic history. Methodology/Principal Findings In this study, the nucleotide polymorphism and the linkage disequilibrium among the complete CRTISO sequence, and the deviation from neutral expectation were analysed by considering population subdivision revealed with 17 microsatellite markers. A sample of 39 accessions, which represented different geographical origins and root colours, was used. Cultivated carrot was divided into two genetic groups: one from Middle East and Asia (Eastern group), and another one mainly from Europe (Western group). The Western and Eastern genetic groups were suggested to be differentially affected by selection: a signature of balancing selection was detected within the first group whereas the second one showed no selection. A focus on orange-rooted carrots revealed that cultivars cultivated in Asia were mainly assigned to the Western group but showed CRTISO haplotypes common to Eastern carrots. Conclusion The carotenoid pathway CRTISO gene data proved to be complementary to neutral markers in order to bring critical insight in the cultivated carrot history. We confirmed the occurrence of two migration events since domestication. Our results showed a European background in material from Japan and Central Asia. While confirming the introduction of European carrots in Japanese resources, the history of Central Asia material remains unclear. PMID:23940644

  9. Gene-environment interaction effects on lung function- a genome-wide association study within the Framingham heart study

    PubMed Central

    2013-01-01

    Background Previous studies in occupational exposure and lung function have focused only on the main effect of occupational exposure or genetics on lung function. Some disease-susceptible genes may be missed due to their low marginal effects, despite potential involvement in the disease process through interactions with the environment. Through comprehensive genome-wide gene-environment interaction studies, we can uncover these susceptibility genes. Our objective in this study was to explore gene by occupational exposure interaction effects on lung function using both the individual SNPs approach and the genetic network approach. Methods The study population comprised the Offspring Cohort and the Third Generation from the Framingham Heart Study. We used forced expiratory volume in one second (FEV1) and ratio of FEV1 to forced vital capacity (FVC) as outcomes. Occupational exposures were classified using a population-specific job exposure matrix. We performed genome-wide gene-environment interaction analysis, using the Affymetrix 550 K mapping array for genotyping. A linear regression-based generalized estimating equation was applied to account for within-family relatedness. Network analysis was conducted using results from single-nucleotide polymorphism (SNP)-level analyses and from gene expression study results. Results There were 4,785 participants in total. SNP-level analysis and network analysis identified SNP rs9931086 (Pinteraction =1.16 × 10-7) in gene SLC38A8, which may significantly modify the effects of occupational exposure on FEV1. Genes identified from the network analysis included CTLA-4, HDAC, and PPAR-alpha. Conclusions Our study implies that SNP rs9931086 in SLC38A8 and genes CTLA-4, HDAC, and PPAR-alpha, which are related to inflammatory processes, may modify the effect of occupational exposure on lung function. PMID:24289273

  10. Knockdown of a Zebrafish Aryl Hydrocarbon Receptor Repressor (AHRRa) Affects Expression of Genes Related to Photoreceptor Development and Hematopoiesis

    PubMed Central

    Aluru, Neelakanteswar; Jenny, Matthew J.; Hahn, Mark E.

    2014-01-01

    The aryl hydrocarbon receptor repressor (AHRR) is a transcriptional repressor of aryl hydrocarbon receptor (AHR) and hypoxia-inducible factor (HIF) and is regulated by an AHR-dependent mechanism. Zebrafish (Danio rerio) possess two AHRR paralogs; AHRRa regulates constitutive AHR signaling during development, whereas AHRRb regulates polyaromatic hydrocarbon-induced gene expression. However, little is known about the endogenous roles and targets of AHRRs. The objective of this study was to elucidate the role of AHRRs during zebrafish development using a loss-of-function approach followed by gene expression analysis. Zebrafish embryos were microinjected with morpholino oligonucleotides against AHRRa or AHRRb to knockdown AHRR protein expression. At 72 h postfertilization (hpf), microarray analysis revealed that the expression of 279 and 116 genes was altered by knockdown of AHRRa and AHRRb, respectively. In AHRRa-morphant embryos, 97 genes were up-regulated and 182 genes were down-regulated. Among the down-regulated genes were several related to photoreceptor function, including cone-specific genes such as several opsins (opn1sw1, opn1sw2, opn1mw1, and opn1lw2), phosphodiesterases (pde6H and pde6C), retinol binding protein (rbp4l), phosducin, and arrestins. Down-regulation was confirmed by RT-PCR and with samples from an independent experiment. The four genes tested (opn1sw1, pde6H, pde6C, and arr3b) were not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AHRRa knockdown also caused up-regulation of embryonic hemoglobin (hbbe3), suggesting a role for AHRR in regulating hematopoiesis. Knockdown of AHRRb caused up-regulation of 31 genes and down-regulation of 85 genes, without enrichment for any specific biological process. Overall, these results suggest that AHRRs may have important roles in development, in addition to their roles in regulating xenobiotic signaling. PMID:24675095

  11. Expression analysis of innate immunity related genes in the true/field blast resistance gene-mediated defence response

    PubMed Central

    Wang, Debing; Qin, Yonghua; Han, Jingluan; Zhang, Ling; Xu, Xin; Liu, Xuequn; Wang, Chuntai; Liu, Xinqiong

    2014-01-01

    Rice blast resistance (R) genes-mediated resistance response depends on various resistance-related genes involved in incompatible interactions. In this work, the expression profiles of innate rice immunity related genes were examined in the mediated resistance response of true/field resistance genes. Three sets of rice near-isogenic lines (NILs) were used: the resistant NILs carrying true resistance genes in the genetic background of the susceptible cultivar Nipponbare (NB), NB-Pib, NB-Pizt, NB-Pik and NB-Pita2; NILs bearing field resistance genes pi21 in the susceptible cultivar Aichiasahi (AA) AA-pi21, Kahei (KHR). The marker gene OsWRKY45 of salicylic acid (SA) signalling was upregulated in all tested cultivars. And, JAmyb (marker gene of jasmonic acid signalling) showed higher upregulation in the resistance lines with nucleotide-binding sites and leucine-rich repeat (NBS-LRR) R genes Pib, Pizt, Pik, Pita2 and Pikahei than in NB and KHS. SalT of abscisic acid (ABA) signalling may be involved in the R/Avr interaction, including Pizt, Pik, pi21 and Pikahei. However, SalT was shown to negatively regulate Pib/AvrPib interaction. OsPR1b and PBZ1 were differentially expressed and strongly activated at a later stage by 48 h post-inoculation. Interestingly, there was evidence that OsPR1b and PBZ1 played an important role in the pi21-mediated response. It was shown that OsRAR1 could be upregulated in the true resistance line NB-Pita2 and the field resistance line KHR, while OsSGT1 and OsHSP90 could be upregulated in all tested lines. The involvement of these genes illustrated the complexity of the downstream signalling pathways in the mediated resistance response of true/field resistance genes.

  12. Quantitative response relationships between degradation rates and functional genes during the degradation of beta-cypermethrin in soil.

    PubMed

    Yang, Zhong-Hua; Ji, Guo-Dong

    2015-12-15

    In the present study, the degradation mechanisms of beta-cypermethrin and its metabolites in soil were explored through the quantitative response relationships between the degradation rates and related functional genes. We found that the degradation rate of beta-cypermethrin was rapid in unsterilized soil but not in sterilized soil, which indicated that the degradation process is microbially based. Moreover, three metabolites (3-phenoxybenzoic acid, phenol and protocatechuic acid) were detected during the degradation process and used to identify the degradation pathway and functional genes related to the degradation process. The key rate-limiting functional genes were pytH and pobA, and the relative contributions of these genes to the degradation process were examined with a path analysis. The path analysis revealed that the genes pobA and pytH had the greatest direct effects on the degradation of beta-cypermethrin (pobA), alpha-cypermethrin (pobA), theta-cypermethrin (pytH) and 3-phenoxybenzoic acid (pytH). PMID:26298261

  13. Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms.

    PubMed

    Le-Niculescu, H; Balaraman, Y; Patel, S D; Ayalew, M; Gupta, J; Kuczenski, R; Shekhar, A; Schork, N; Geyer, M A; Niculescu, A B

    2011-01-01

    Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug--yohimbine, and an anti-anxiety drug--diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR and DBP), brain-blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders--notably signal transduction and reactivity to environment, with a prominent role for the hippocampus. Overall, this work complements our previous similar work (on bipolar mood disorders and schizophrenia) conducted over the last decade. It concludes our programmatic first pass mapping of the genomic landscape of the triad of major psychiatric disorder domains using CFG, and permitted us to uncover the significant genetic overlap between anxiety and these other major psychiatric disorders, notably the under-appreciated overlap with schizophrenia. PDE10A, TAC1 and other genes uncovered by our work provide a molecular basis for the frequently observed clinical co-morbidity and interdependence between anxiety and other major psychiatric disorders, and suggest schizo-anxiety as a possible new nosological domain. PMID:22832404

  14. The functional diversity of essential genes required for mammalian cardiac development

    PubMed Central

    Clowes, Christopher; Boylan, Michael GS; Ridge, Liam A; Barnes, Emma; Wright, Jayne A; Hentges, Kathryn E

    2014-01-01

    Genes required for an organism to develop to maturity (for which no other gene can compensate) are considered essential. The continuing functional annotation of the mouse genome has enabled the identification of many essential genes required for specific developmental processes including cardiac development. Patterns are now emerging regarding the functional nature of genes required at specific points throughout gestation. Essential genes required for development beyond cardiac progenitor cell migration and induction include a small and functionally homogenous group encoding transcription factors, ligands and receptors. Actions of core cardiogenic transcription factors from the Gata, Nkx, Mef, Hand, and Tbx families trigger a marked expansion in the functional diversity of essential genes from midgestation onwards. As the embryo grows in size and complexity, genes required to maintain a functional heartbeat and to provide muscular strength and regulate blood flow are well represented. These essential genes regulate further specialization and polarization of cell types along with proliferative, migratory, adhesive, contractile, and structural processes. The identification of patterns regarding the functional nature of essential genes across numerous developmental systems may aid prediction of further essential genes and those important to development and/or progression of disease. genesis 52:713–737, 2014. PMID:24866031

  15. Discovery of Genes Related to Witches Broom Disease in Paulownia tomentosa × Paulownia fortunei by a De Novo Assembled Transcriptome

    PubMed Central

    Liu, Rongning; Dong, Yanpeng; Fan, Guoqiang; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Niu, Suyan

    2013-01-01

    In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches’ Broom (PaWB) disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene’s roles in the developmental process and in PaWB disease resistance. PMID:24278262

  16. Function and mechanism of tumor suppressor gene LRRC4/NGL-2.

    PubMed

    Li, Peiyao; Xu, Gang; Li, Guiyuan; Wu, Minghua

    2014-01-01

    LRRC4/NGL-2 (Leucine rich repeat containing 4/Netrin-G ligand-2), a relatively specific expressed gene in brain tissue, is a member of the LRRC4/ NGL (netrin-G ligand) family and belongs to the superfamily of LRR proteins. LRRC4/NGL-2 regulates neurite outgrowth and lamina-specific dendritic segmentation, suggesting that LRRC4/NGL-2 is important for the development of the nervous system. In addition, LRRC4/NGL-2 has been identified as a tumor suppressor gene. The overexpression of LRRC4/NGL-2 suppresses glioma cell growth, angiogenesis and invasion through complicated signaling regulation networks. LRRC4/NGL-2 also has the ability to form multiphase loops with miRNA, transcription factors and gene methylation modification; the loss of LRRC4/NGL-2 function may be an important event in multiple biological processes in gliomas. In summary, LRRC4/NGL-2 is a critical gene in the normal development and tumorigenesis of the nervous system. PMID:25526788

  17. Multiple Thyrotropin ?-Subunit and Thyrotropin Receptor-Related Genes Arose during Vertebrate Evolution

    PubMed Central

    Maugars, Gersende; Dufour, Sylvie; Cohen-Tannoudji, Joëlle; Quérat, Bruno

    2014-01-01

    Thyroid-stimulating hormone (TSH) is composed of a specific ? subunit and an ? subunit that is shared with the two pituitary gonadotropins. The three ? subunits derive from a common ancestral gene through two genome duplications (1R and 2R) that took place before the radiation of vertebrates. Analysis of genomic data from phylogenetically relevant species allowed us to identify an additional Tsh? subunit-related gene that was generated through 2R. This gene, named Tsh?2, present in cartilaginous fish, little skate and elephant shark, and in early lobe-finned fish, coelacanth and lungfish, was lost in ray-finned fish and tetrapods. The absence of a second type of TSH receptor (Tshr) gene in these species suggests that both TSHs act through the same receptor. A novel Tsh? sister gene, named Tsh?3, was generated through the third genomic duplication (3R) that occurred early in the teleost lineage. Tsh?3 is present in most teleost groups but was lostin tedraodontiforms. The 3R also generated a second Tshr, named Tshrb. Interestingly, the new Tshrb was translocated from its original chromosomic position after the emergence of eels and was then maintained in its new position. Tshrb was lost in tetraodontiforms and in ostariophysians including zebrafish although the latter species have two TSHs, suggesting that TSHRb may be dispensable. The tissue distribution of duplicated Tsh?s and Tshrs was studied in the European eel. The endocrine thyrotropic function in the eel would be essentially mediated by the classical Tsh? and Tshra, which are mainly expressed in the pituitary and thyroid, respectively. Tsh?3 and Tshrb showed a similar distribution pattern in the brain, pituitary, ovary and adipose tissue, suggesting a possible paracrine/autocrine mode of action in these non-thyroidal tissues. Further studies will be needed to determine the binding specificity of the two receptors and how these two TSH systems are interrelated. PMID:25386660

  18. Multiple thyrotropin ?-subunit and thyrotropin receptor-related genes arose during vertebrate evolution.

    PubMed

    Maugars, Gersende; Dufour, Sylvie; Cohen-Tannoudji, Joëlle; Quérat, Bruno

    2014-01-01

    Thyroid-stimulating hormone (TSH) is composed of a specific ? subunit and an ? subunit that is shared with the two pituitary gonadotropins. The three ? subunits derive from a common ancestral gene through two genome duplications (1R and 2R) that took place before the radiation of vertebrates. Analysis of genomic data from phylogenetically relevant species allowed us to identify an additional Tsh? subunit-related gene that was generated through 2R. This gene, named Tsh?2, present in cartilaginous fish, little skate and elephant shark, and in early lobe-finned fish, coelacanth and lungfish, was lost in ray-finned fish and tetrapods. The absence of a second type of TSH receptor (Tshr) gene in these species suggests that both TSHs act through the same receptor. A novel Tsh? sister gene, named Tsh?3, was generated through the third genomic duplication (3R) that occurred early in the teleost lineage. Tsh?3 is present in most teleost groups but was lostin tedraodontiforms. The 3R also generated a second Tshr, named Tshrb. Interestingly, the new Tshrb was translocated from its original chromosomic position after the emergence of eels and was then maintained in its new position. Tshrb was lost in tetraodontiforms and in ostariophysians including zebrafish although the latter species have two TSHs, suggesting that TSHRb may be dispensable. The tissue distribution of duplicated Tsh?s and Tshrs was studied in the European eel. The endocrine thyrotropic function in the eel would be essentially mediated by the classical Tsh? and Tshra, which are mainly expressed in the pituitary and thyroid, respectively. Tsh?3 and Tshrb showed a similar distribution pattern in the brain, pituitary, ovary and adipose tissue, suggesting a possible paracrine/autocrine mode of action in these non-thyroidal tissues. Further studies will be needed to determine the binding specificity of the two receptors and how these two TSH systems are interrelated. PMID:25386660

  19. Functional and evolutionary analyses on expressed intronless genes in the mouse genome

    SciTech Connect

    Sakharkar, K R; Sakharkar, M K; Culiat, Cymbeline T; Chow, V T K; Pervaiz, S

    2006-01-01

    Using computational approaches we have identified 2017 expressed intronless genes in the mouse genome. Evolutionary analysis reveals that 56 intronless genes are conserved among the three domains of life - bacteria, archea and eukaryotes. These highly conserved intronless genes were found to be involved in essential housekeeping functions. About 80% of expressed mouse intronless genes have orthologs in eukaryotic genomes only, and thus are specific to eukaryotic organisms. 608 of these genes have intronless human orthologs and 302 of these orthologs have a match in OMIM database. Investigation into these mouse genes will be important in generating mouse models for understanding human diseases.

  20. Transcriptome-Wide Differential Gene Expression in Bicyclus anynana Butterflies: Female Vision-Related Genes Are More Plastic.

    PubMed

    Macias-Muñoz, Aide; Smith, Gilbert; Monteiro, Antónia; Briscoe, Adriana D

    2016-01-01

    Vision is energetically costly to maintain. Consequently, over time many cave-adapted species downregulate the expression of vision genes or even lose their eyes and associated eye genes entirely. Alternatively, organisms that live in fluctuating environments, with different requirements for vision at different times, may evolve phenotypic plasticity for expression of vision genes. Here, we use a global transcriptomic and candidate gene approach to compare gene expression in the heads of a polyphenic butterfly. Bicyclus anynana have two seasonal forms that display sexual dimorphism and plasticity in eye morphology, and female-specific plasticity in opsin gene expression. Nonchoosy dry season females downregulate opsin expression, consistent with the high physiological cost of vision. To identify other genes associated with sexually dimorphic and seasonally plastic differences in vision, we analyzed RNA-sequencing data from whole head tissues. We identified two eye development genes (klarsicht and warts homologs) and an eye pigment biosynthesis gene (henna) differentially expressed between seasonal forms. By comparing sex-specific expression across seasonal forms, we found that klarsicht, warts, henna, and another eye development gene (domeless) were plastic in a female-specific manner. In a male-only analysis, white (w) was differentially expressed between seasonal forms. Reverse transcription polymerase chain reaction confirmed that warts and white are expressed in eyes only, whereas klarsicht, henna and domeless are expressed in both eyes and brain. We find that differential expression of eye development and eye pigment genes is associated with divergent eye phenotypes in B. anynana seasonal forms, and that there is a larger effect of season on female vision-related genes. PMID:26371082

  1. Structure–activity relationships for ?-calcitonin gene-related peptide

    PubMed Central

    Watkins, Harriet A; Rathbone, Dan L; Barwell, James; Hay, Debbie L; Poyner, David R

    2013-01-01

    Calcitonin gene-related peptide (CGRP) is a member of the calcitonin (CT) family of peptides. It is a widely distributed neuropeptide implicated in conditions such as neurogenic inflammation. With other members of the CT family, it shares an N-terminal disulphide-bonded ring which is essential for biological activity, an area of potential ?-helix, and a C-terminal amide. CGRP binds to the calcitonin receptor-like receptor (CLR) in complex with receptor activity-modifying protein 1 (RAMP1), a member of the family B (or secretin-like) GPCRs. It can also activate other CLR or calcitonin-receptor/RAMP complexes. This 37 amino acid peptide comprises the N-terminal ring that is required for receptor activation (residues 1–7); an ?-helix (residues 8–18), a region incorporating a ?-bend (residues 19–26) and the C-terminal portion (residues 27–37), that is characterized by bends between residues 28–30 and 33–34. A few residues have been identified that seem to make major contributions to receptor binding and activation, with a larger number contributing either to minor interactions (which collectively may be significant), or to maintaining the conformation of the bound peptide. It is not clear if CGRP follows the pattern of other family B GPCRs in binding largely as an ?-helix. LINKED ARTICLES This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 PMID:23186257

  2. Identification and functional characterization of two new transcriptional variants of the human p63 gene

    PubMed Central

    Mangiulli, Marina; Valletti, Alessio; Caratozzolo, Mariano Francesco; Tullo, Apollonia; Sbisà, Elisabetta; Pesole, Graziano; D’Erchia, Anna Maria

    2009-01-01

    p63 belongs to a family of transcription factors, which, while demonstrating striking conservation of functional domains, regulate distinct biological functions. Its principal role is in the regulation of epithelial commitment, differentiation and maintenance programs, during embryogenesis and in adult tissues. The p63 gene has a complex transcriptional pattern, producing two subclasses of N-terminal isoforms (TA and ?N) which are alternatively spliced at the C-terminus. Here, we report the identification of two new C-terminus p63 variants, we named p63 ? and ?, that increase from 6 to 10 the number of the p63 isoforms. Expression analysis of all p63 variants demonstrates a tissue/cell-type-specific nature of p63 alternative transcript expression, probably related to their different cellular functions. We demonstrate that the new p63 variants as ?N isoforms are active as transcription factors as they have nuclear localization and can modulate the expression of p63 target genes. Moreover, we report that, like ?Np63?, ?Np63? and ? sustain cellular proliferation and that their expression decreases during keratinocyte differentiation, suggesting their involvement in this process. Taken together, our results demonstrate the existence of novel p63 proteins whose expression should be considered in future studies on the roles of p63 in the regulation of cellular functions. PMID:19700772

  3. Functional and conserved domains of the Drosophila transcription factor encoded by the segmentation gene knirps.

    PubMed Central

    Gerwin, N; La Rosée, A; Sauer, F; Halbritter, H P; Neumann, M; Jäckle, H; Nauber, U

    1994-01-01

    The Drosophila gap gene knirps (kni) is required for abdominal segmentation. It encodes a steroid/thyroid orphan receptor-type transcription factor which is distributed in a broad band of nuclei in the posterior region of the blastoderm. To identify essential domains of the kni protein (KNI), we cloned and sequenced the DNA encompassing the coding region of nine kni mutant alleles of different strength and kni-homologous genes of related insect species. We also examined in vitro-modified versions of KNI in various assay systems both in vitro and in tissue culture. The results show that KNI contains several functional domains which are arranged in a modular fashion. The N-terminal 185-amino-acid region which includes the DNA-binding domain and a functional nuclear location signal fails to provide kni activity to the embryo. However, a truncated KNI protein that contains additional 47 amino acids exerts rather strong kni activity which is functionally defined by a weak kni mutant phenotype of the embryo. The additional 47-amino-acid stretch includes a transcriptional repressor domain which acts in the context of a heterologous DNA-binding domain of the yeast transcriptional activator GAL4. The different domains of KNI as defined by functional studies are conserved during insect evolution. Images PMID:7969130

  4. Separable roles of UFO during floral development revealed by conditional restoration of gene function.

    PubMed

    Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John

    2003-02-01

    The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia. PMID:12506008

  5. Incorporating gene functions into regression analysis of DNA-protein binding data and gene expression data to construct transcriptional networks.

    PubMed

    Wei, Peng; Pan, Wei

    2008-01-01

    Useful information on transcriptional networks has been extracted by regression analyses of gene expression data and DNA-protein binding data. However, a potential limitation of these approaches is their assumption on the common and constant activity level of a transcription factor (TF) on all the genes in any given experimental condition; for example, any TF is assumed to be either an activator or a repressor, but not both, while it is known that some TFs can be dual regulators. Rather than assuming a common linear regression model for all the genes, we propose using separate regression models for various gene groups; the genes can be grouped based on their functions or some clustering results. Furthermore, to take advantage of the hierarchical structure of many existing gene function annotation systems, such as Gene Ontology (GO), we propose a shrinkage method that borrows information from relevant gene groups. Applications to a yeast dataset and simulations lend support for our proposed methods. In particular, we find that the shrinkage method consistently works well under various scenarios. We recommend the use of the shrinkage method as a useful alternative to the existing methods. PMID:18670043

  6. Evaluation of high-throughput functional categorization of human disease genes

    PubMed Central

    Chen, James L; Liu, Yang; Sam, Lee T; Li, Jianrong; Lussier, Yves A

    2007-01-01

    Background Biological data that are well-organized by an ontology, such as Gene Ontology, enables high-throughput availability of the semantic web. It can also be used to facilitate high throughput classification of biomedical information. However, to our knowledge, no evaluation has been published on automating classifications of human diseases genes using Gene Ontology. In this study, we evaluate automated classifications of well-defined human disease genes using their Gene Ontology annotations and compared them to a gold standard. This gold standard was independently conceived by Valle's research group, and contains 923 human disease genes organized in 14 categories of protein function. Results Two automated methods were applied to investigate the classification of human disease genes into independently pre-defined categories of protein function. One method used the structure of Gene Ontology by pre-selecting 74 Gene Ontology terms assigned to 11 protein function categories. The second method was based on the similarity of human disease genes clustered according to the information-theoretic distance of their Gene Ontology annotations. Compared to the categorization of human disease genes found in the gold standard, our automated methods can achieve an overall 56% and 47% precision with 62% and 71% recall respectively. However, approximately 15% of the studied human disease genes remain without GO annotations. Conclusion Automated methods can recapitulate a significant portion of classification of the human disease genes. The method using information-theoretic distance performs slightly better on the precision with some loss in recall. For some protein function categories, such as 'hormone' and 'transcription factor', the automated methods perform particularly well, achieving precision and recall levels above 75%. In summary, this study demonstrates that for semantic webs, methods to automatically classify or analyze a majority of human disease genes require significant progress in both the Gene Ontology annotations and particularly in the utilization of these annotations. PMID:17493290

  7. Pigmentary function and evolution of tyrp1 gene duplicates in fish.

    PubMed

    Braasch, Ingo; Liedtke, Daniel; Volff, Jean-Nicolas; Schartl, Manfred

    2009-12-01

    The function of the tyrosinase-related protein 1 (Tyrp1) has not yet been investigated in vertebrates basal to tetrapods. Teleost fishes have two duplicates of the tyrp1 gene. Here, we show that the teleost tyrp1 duplicates have distributed the ancestral gene expression in the retinal pigment epithelium (RPE) and melanophores in a species-specific manner. In medaka embryos, tyrp1a expression is found in the RPE and in melanophores while tyrp1b is only expressed in melanophores. In zebrafish embryos, expression of tyrp1 paralogs overlaps in the RPE and in melanophores. Knockdown of each zebrafish tyrp1 duplicate alone does not show pigmentary defects, but simultaneous knockdown of both tyrp1 genes results in the formation of brown instead of black eumelanin accompanied by severe melanosome defects. Our study suggests that the brown melanosome color in Tyrp1-deficient vertebrates is an effect of altered eumelanin synthesis. Black eumelanin formation essentially relies on the presence of Tyrp1 and some of its function is most likely conserved from the common ancestor of bony vertebrates. PMID:19659755

  8. Functional dissection of Odorant binding protein genes in Drosophila melanogaster.

    PubMed

    Swarup, S; Williams, T I; Anholt, R R H

    2011-08-01

    Most organisms rely on olfaction for survival and reproduction. The olfactory system of Drosophila melanogaster is one of the best characterized chemosensory systems and serves as a prototype for understanding insect olfaction. Olfaction in Drosophila is mediated by multigene families of odorant receptors and odorant binding proteins (OBPs). Although molecular response profiles of odorant receptors have been well documented, the contributions of OBPs to olfactory behavior remain largely unknown. Here, we used RNAi-mediated suppression of Obp gene expression and measurements of behavioral responses to 16 ecologically relevant odorants to systematically dissect the functions of 17 OBPs. We quantified the effectiveness of RNAi-mediated suppression by quantitative real-time polymerase chain reaction and used a proteomic liquid chromatography and tandem mass spectrometry procedure to show target-specific suppression of OBPs expressed in the antennae. Flies in which expression of a specific OBP is suppressed often show altered behavioral responses to more than one, but not all, odorants, in a sex-dependent manner. Similarly, responses to a specific odorant are frequently affected by suppression of expression of multiple, but not all, OBPs. These results show that OBPs are essential for mediating olfactory behavioral responses and suggest that OBP-dependent odorant recognition is combinatorial. PMID:21605338

  9. Regional Homogeneity of Resting-State Brain Activity Suppresses the Effect of Dopamine-Related Genes on Sensory Processing Sensitivity

    PubMed Central

    Chen, Chuansheng; Moyzis, Robert; Xia, Mingrui; He, Yong; Xue, Gui; Li, Jin; He, Qinghua; Lei, Xuemei; Wang, Yunxin; Liu, Bin; Chen, Wen; Zhu, Bi; Dong, Qi

    2015-01-01

    Sensory processing sensitivity (SPS) is an intrinsic personality trait whose genetic and neural bases have recently been studied. The current study used a neural mediation model to explore whether resting-state brain functions mediated the effects of dopamine-related genes on SPS. 298 healthy Chinese college students (96 males, mean age = 20.42 years, SD = 0.89) were scanned with magnetic resonance imaging during resting state, genotyped for 98 loci within the dopamine system, and administered the Highly Sensitive Person Scale. We extracted a “gene score” that summarized the genetic variations representing the 10 loci that were significantly linked to SPS, and then used path analysis to search for brain regions whose resting-state data would help explain the gene-behavior association. Mediation analysis revealed that temporal homogeneity of regional spontaneous activity (ReHo) in the precuneus actually suppressed the effect of dopamine-related genes on SPS. The path model explained 16% of the variance of SPS. This study represents the first attempt at using a multi-gene voxel-based neural mediation model to explore the complex relations among genes, brain, and personality. PMID:26308205

  10. [Cloning and regulation of pig estrogen related receptor ? gene (ESRRB) promoter].

    PubMed

    Yang, Yang; Wang, Yaxian; Du, Lixia; Wang, Huayan

    2015-04-01

    The estrogen related receptor family member Esrrb (Estrogen related receptor ?) is a gene that expresses in the early stage of embryo and plays an important role in the core pluripotent network. Its function has been analyzed in human and mouse, although no report so far related to pig. Therefore, to explore its mechanism of transcriptional regulation and expression pattern, we cloned a 3.3 kb pig ESRRB promoter by PCR and constructed the green fluorescence protein (GFP) reporter vector pE3.3. We used these vectors to study the ESRRB expression pattern in 293T, Hela and C2C12. Sequence was analyzed for regulatory elements that share homology to known transcription factor binding sites by TFSEARCH and JASPER program. Some pluripotency related genes such as SMAD, STAT3, MYC, KLF4 and ESRRB have been found within the 3.3 kb sequence by co-transfected pig ESRRB promoter and these potential regulators. We found that ESRRB only expressed in 293T and SMAD could activate ESRRB expression obviously. To determine the core promoter region, a series of ESRRB promoter fragments with gradually truncated 5'-end were produced by PCR and inserted into pGL3-Basic vector. After transient transfection into 293T, dual luciferase assay was used to measure these promoter activities. The result suggested that the core promoter of pig ESRRB located within -25 bp to -269 bp region. These results suggest that these transcription factor binding sites and the core promoter region may be essential for transcriptional regulation of pig ESRRB gene. PMID:26380406

  11. DCEG Scientists Identify New Gene Mutation Related to Familial Melanoma

    Cancer.gov

    Scientists have identified a rare inherited mutation in a gene that can increase the risk of familial melanoma, according to a study that appeared online in Nature Genetics on March 30, 2014. Although the finding does not offer immediate benefit to patients, variation in the Protection of Telomeres-1 (POT1) gene provides additional clues as to the origins of melanoma and may open new avenues in prevention and treatment research.

  12. Progestin-Containing Contraceptives Alter Expression of Host Defense-Related Genes of the Endometrium and Cervix.

    PubMed

    Goldfien, Gabriel A; Barragan, Fatima; Chen, Joseph; Takeda, Margaret; Irwin, Juan C; Perry, Jean; Greenblatt, Ruth M; Smith-McCune, Karen K; Giudice, Linda C

    2015-07-01

    Epidemiological studies indicate that progestin-containing contraceptives increase susceptibility to HIV, although the underlying mechanisms involving the upper female reproductive tract are undefined. To determine the effects of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) on gene expression and physiology of human endometrial and cervical transformation zone (TZ), microarray analyses were performed on whole tissue biopsies. In endometrium, activated pathways included leukocyte chemotaxis, attachment, and inflammation in DMPA and LNG-IUS users, and individual genes included pattern recognition receptors, complement components, and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability but not immune function genes. Together, these results indicate that progestins influence expression of immune-related genes in endometrium relevant to local recruitment of HIV target cells with potential to increase susceptibility and underscore the importance of the upper reproductive tract when assessing the safety of contraceptive products. PMID:25634912

  13. Microarrays of lentiviruses for gene function screens in immortalized and primary cells

    E-print Network

    Cai, Long

    ) or an shRNA targeting human lamin A/C8. We seeded 2 Â 106 HeLa cells onto the array and, after 72 hMicroarrays of lentiviruses for gene function screens in immortalized and primary cells Steve N-infected cell microarrays for the high-throughput screening of gene function in mammalian cells. To create

  14. Plasticity of the cis-Regulatory Input Function of a Gene

    E-print Network

    of the CRIF of a well- characterized gene system, the lac operon [19­21] of Escherichia coli, was obtained operon of Escherichia coli, which has an elaborate input function, intermediate between Boolean ANDPlasticity of the cis-Regulatory Input Function of a Gene Avraham E. Mayo¤ , Yaakov Setty, Seagull

  15. Estrogen receptor gene expression in relation to neuropsychiatric disorders.

    PubMed

    Ostlund, Hanna; Keller, Eva; Hurd, Yasmin L

    2003-12-01

    Compelling evidence now exists for estrogen's involvement in the regulation of mood and cognitive functions. Serum estrogen levels have been shown to play an important role in the expression of psychiatric disorders such as depression and schizophrenia. We have characterized the distribution of the estrogen receptors, ERalpha and ERbeta, in the human brain and showed a preferential limbic-related expression pattern for these transcripts. The ERalpha mRNA dominates in the amygdala and hypothalamus, suggesting estrogen modulation of autonomic and neuroendocrine as well as emotional functions. In contrast, the hippocampal formation, entorhinal cortex, and thalamus appear to be ERbeta-dominant areas, suggesting a role for ERbeta in cognition, non-emotional memory, and motor functions. The role of estradiol can also be examined in regard to its relationship to other neurotransmitter systems known to be linked to specific psychiatric disorders. Estradiol has been shown to regulate the serotonin (5-HT) system, which has been strongly implicated in affective disorders. We have studied a genetic animal model of depression, and found altered 5-HT receptor mRNA levels in discrete brain regions; many of the abnormalities are reversed by estradiol treatment, especially for the 5-HT(2A) receptor subtype. The norepinephrine (NE) system is, similar to serotonin, a target for antidepressant drugs, and projects to mesocorticolimbic structures implicated in mood disorders. We have recently observed that NE neurons in the human locus coeruleus (LC) express moderate levels of both ER transcripts. The possibility of estrogen's regulating LC function has been documented in animal studies. Results from our preliminary experiments have revealed that the ERbeta mRNA is decreased in persons committing suicide, a cause of death that is highly linked to affective disorder. Follow-up studies are currently under way with a much larger population to validate these results. Overall, the discrete anatomical organization of the ER mRNAs in the human brain provide evidence as to the specific neuronal populations in which the actions of ERs could modulate mood and thus underlie the neuropathology of psychiatric disorders such as depression. PMID:14993040

  16. Shifts of functional gene representation in wheat rhizosphere microbial communities under elevated ozone

    PubMed Central

    Li, Xinyu; Deng, Ye; Li, Qi; Lu, Caiyan; Wang, Jingjing; Zhang, Huiwen; Zhu, Jianguo; Zhou, Jizhong; He, Zhili

    2013-01-01

    Although the influence of ozone (O3) on plants has been well studied in agroecosystems, little is known about the effect of elevated O3 (eO3) on soil microbial functional communities. Here, we used a comprehensive functional gene array (GeoChip 3.0) to investigate the functional composition, and structure of rhizosphere microbial communities of Yannong 19 (O3-sensitive) and Yangmai 16 (O3-relatively sensitive) wheat (Triticum aestivum L.) cultivars under eO3. Compared with ambient O3 (aO3), eO3 led to an increase in soil pH and total carbon (C) percentages in grain and straw of wheat plants, and reduced grain weight and soil dissolved organic carbon (DOC). Based on GeoChip hybridization signal intensities, although the overall functional structure of rhizosphere microbial communities did not significantly change by eO3 or cultivars, the results showed that the abundance of specific functional genes involved in C fixation and degradation, nitrogen (N) fixation, and sulfite reduction did significantly (P<0.05) alter in response to eO3 and/or wheat cultivars. Also, Yannong 19 appeared to harbor microbial functional communities in the rhizosphere more sensitive in response to eO3 than Yangmai 16. Additionally, canonical correspondence analysis suggested that the functional structure of microbial community involved in C cycling was largely shaped by soil and plant properties including pH, DOC, microbial biomass C, C/N ratio and grain weight. This study provides new insight into our understanding of the influence of eO3 and wheat cultivars on soil microbial communities. PMID:23151639

  17. Hermes, a Functional Non-Drosophilid Insect Gene Vector from Musca Domestica

    PubMed Central

    O'Brochta, D. A.; Warren, W. D.; Saville, K. J.; Atkinson, P. W.

    1996-01-01

    Hermes is a short inverted repeat-type transposable element from the house fly, Musca domestica. Using an extra-chromosomal transpositional recombination assay, we show that Hermes elements can accurately transpose in M. domestica embryos. To test the ability of Hermes to function in species distantly related to M. domestica we used a nonautonomous Hermes element containing the Drosophila melanogaster white (w(+)) gene and created D. melanogaster germline transformants. Transgenic G(1) insects were recovered from 34.6% of the fertile G(0) adults developing from microinjected w(-) embryos. This transformation rate is comparable with that observed using P or hobo vectors in D. melanogaster, however, many instances of multiple-element insertions and large clusters were observed. Genetic mapping, Southern blotting, polytene chromosome in situ hybridization and DNA sequence analyses confirmed that Hermes elements were chromosomally integrated in transgenic insects. Our data demonstrate that Hermes elements transpose at high rates in D. melanogaster and may be an effective gene vector and gene-tagging agent in this species and distantly related species of medical and agricultural importance. PMID:8849896

  18. Using CATH-Gene3D to Analyze the Sequence, Structure, and Function of Proteins.

    PubMed

    Sillitoe, Ian; Lewis, Tony; Orengo, Christine

    2015-01-01

    The CATH database is a classification of protein structures found in the Protein Data Bank (PDB). Protein structures are chopped into individual units of structural domains, and these domains are grouped together into superfamilies if there is sufficient evidence that they have diverged from a common ancestor during the process of evolution. A sister resource, Gene3D, extends this information by scanning sequence profiles of these CATH domain superfamilies against many millions of known proteins to identify related sequences. Thus the combined CATH-Gene3D resource provides confident predictions of the likely structural fold, domain organisation, and evolutionary relatives of these proteins. In addition, this resource incorporates annotations from a large number of external databases such as known enzyme active sites, GO molecular functions, physical interactions, and mutations. This unit details how to access and understand the information contained within the CATH-Gene3D Web pages, the downloadable data files, and the remotely accessible Web services. © 2015 by John Wiley & Sons, Inc. PMID:26087950

  19. Bioinformatic prediction of gene functions regulated by quorum sensing in the bioleaching bacterium Acidithiobacillus ferrooxidans.

    PubMed

    Banderas, Alvaro; Guiliani, Nicolas

    2013-01-01

    The biomining bacterium Acidithiobacillus ferrooxidans oxidizes sulfide ores and promotes metal solubilization. The efficiency of this process depends on the attachment of cells to surfaces, a process regulated by quorum sensing (QS) cell-to-cell signalling in many Gram-negative bacteria. At. ferrooxidans has a functional QS system and the presence of AHLs enhances its attachment to pyrite. However, direct targets of the QS transcription factor AfeR remain unknown. In this study, a bioinformatic approach was used to infer possible AfeR direct targets based on the particular palindromic features of the AfeR binding site. A set of Hidden Markov Models designed to maintain palindromic regions and vary non-palindromic regions was used to screen for putative binding sites. By annotating the context of each predicted binding site (PBS), we classified them according to their positional coherence relative to other putative genomic structures such as start codons, RNA polymerase promoter elements and intergenic regions. We further used the Multiple EM for Motif Elicitation algorithm (MEME) to further filter out low homology PBSs. In summary, 75 target-genes were identified, 34 of which have a higher confidence level. Among the identified genes, we found afeR itself, zwf, genes encoding glycosyltransferase activities, metallo-beta lactamases, and active transport-related proteins. Glycosyltransferases and Zwf (Glucose 6-phosphate-1-dehydrogenase) might be directly involved in polysaccharide biosynthesis and attachment to minerals by At. ferrooxidans cells during the bioleaching process. PMID:23959118

  20. Bioinformatic Prediction of Gene Functions Regulated by Quorum Sensing in the Bioleaching Bacterium Acidithiobacillus ferrooxidans

    PubMed Central

    Banderas, Alvaro; Guiliani, Nicolas

    2013-01-01

    The biomining bacterium Acidithiobacillus ferrooxidans oxidizes sulfide ores and promotes metal solubilization. The efficiency of this process depends on the attachment of cells to surfaces, a process regulated by quorum sensing (QS) cell-to-cell signalling in many Gram-negative bacteria. At. ferrooxidans has a functional QS system and the presence of AHLs enhances its attachment to pyrite. However, direct targets of the QS transcription factor AfeR remain unknown. In this study, a bioinformatic approach was used to infer possible AfeR direct targets based on the particular palindromic features of the AfeR binding site. A set of Hidden Markov Models designed to maintain palindromic regions and vary non-palindromic regions was used to screen for putative binding sites. By annotating the context of each predicted binding site (PBS), we classified them according to their positional coherence relative to other putative genomic structures such as start codons, RNA polymerase promoter elements and intergenic regions. We further used the Multiple EM for Motif Elicitation algorithm (MEME) to further filter out low homology PBSs. In summary, 75 target-genes were identified, 34 of which have a higher confidence level. Among the identified genes, we found afeR itself, zwf, genes encoding glycosyltransferase activities, metallo-beta lactamases, and active transport-related proteins. Glycosyltransferases and Zwf (Glucose 6-phosphate-1-dehydrogenase) might be directly involved in polysaccharide biosynthesis and attachment to minerals by At. ferrooxidans cells during the bioleaching process. PMID:23959118

  1. Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension

    PubMed Central

    Nikkari, Seppo T.; Määttä, Kirsi M.; Kunnas, Tarja A.

    2015-01-01

    Abstract Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.–1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort. This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression. At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P?=?0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR?=?1.47; CI?=?1.08–2.01; P?=?0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI]?=?1.20–12.27; P?=?0.024). Those carrying variant A had also significantly higher readings of both systolic (P?=?0.047) and diastolic (P?=?0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA–GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR?=?2.01; CI?=?1.29–3.12; P?=?0.002). In conclusion, there was a significant association between iNOS genetic variant (rs2779249) and hypertension in the genetically homogenous Finnish population. Those who carried the rare A-allele of the gene had higher risk for hypertension already at the age of 35 years. PMID:26579803

  2. A computational procedure for functional characterization of potential marker genes from molecular data: Alzheimer's as a case study

    PubMed Central

    2011-01-01

    Background A molecular characterization of Alzheimer's Disease (AD) is the key to the identification of altered gene sets that lead to AD progression. We rely on the assumption that candidate marker genes for a given disease belong to specific pathogenic pathways, and we aim at unveiling those pathways stable across tissues, treatments and measurement systems. In this context, we analyzed three heterogeneous datasets, two microarray gene expression sets and one protein abundance set, applying a recently proposed feature selection method based on regularization. Results For each dataset we identified a signature that was successively evaluated both from the computational and functional characterization viewpoints, estimating the classification error and retrieving the most relevant biological knowledge from different repositories. Each signature includes genes already known to be related to AD and genes that are likely to be involved in the pathogenesis or in the disease progression. The integrated analysis revealed a meaningful overlap at the functional level. Conclusions The identification of three gene signatures showing a relevant overlap of pathways and ontologies, increases the likelihood of finding potential marker genes for AD. PMID:21726470

  3. Evolutionary History and Functional Characterization of Three Large Genes Involved in Sporulation in Bacillus cereus Group Bacteria?†

    PubMed Central

    Reiter, Lillian; Tourasse, Nicolas J.; Fouet, Agnès; Loll, Raphaël; Davison, Sophie; Økstad, Ole Andreas; Piehler, Armin P.; Kolstø, Anne-Brit

    2011-01-01

    The Bacillus cereus group of bacteria is a group of closely related species that are of medical and economic relevance, including B. anthracis, B. cereus, and B. thuringiensis. Bacteria from the Bacillus cereus group encode three large, highly conserved genes of unknown function (named crdA, crdB, and crdC) that are composed of 16 to 35 copies of a repeated domain of 132 amino acids at the protein level. Bioinformatic analysis revealed that there is a phylogenetic bias in the genomic distribution of these genes and that strains harboring all three large genes mainly belong to cluster III of the B. cereus group phylogenetic tree. The evolutionary history of the three large genes implicates gain, loss, duplication, internal deletion, and lateral transfer. Furthermore, we show that the transcription of previously identified antisense open reading frames in crdB is simultaneously regulated with its host gene throughout the life cycle in vitro, with the highest expression being at the onset of sporulation. In B. anthracis, different combinations of double- and triple-knockout mutants of the three large genes displayed slower and less efficient sporulation processes than the parental strain. Altogether, the functional studies suggest an involvement of these three large genes in the sporulation process. PMID:21821775

  4. Gene Networks and Functional Features of Gravitropic response in Rice Shoot Bases

    NASA Astrophysics Data System (ADS)

    Hu, Liwei; Zang, Aiping; Ai, Qianru; Chen, Haiying; Li, Lin; Li, Rui; Su, Feng; Chen, Xijiang; Rong, Hui; Dou, Xianying; Reinhold-Hurek, Barbara; Li, Qi; Cai, Weiming

    To delineate key genes and the corresponding physiological functions as well as the coordina-tion of genes involved in the gravitropism of rice shoot bases, we used whole-genome microarray analysis of upper and lower parts of rice shoot bases at 0.5 h and 6 h after gravistimulation. And bio-information analysis was applied including GO-analysis, expression tendency and net-work analysis. In the lower shoot bases, auxin-mediated signaling pathway and glutathione transferase activity with the biggest enrichment were activated at 0.5 h, while cytokinin stimu-lus and photosynthesis were activated at 6 h. Meanwhile, several processes were suppressed in the lower shoot bases, including: xyloglucan:xyloglucosyl transferase activity, glucan metabolic processes, and ATPase activity at 0.5 h; and tRNA isopentenyltransferase activity, and chiti-nase activity, etc. at 6 h. Gene expression profile responding to gravistimulation suggested that the asymmetrically activation of several phytohormone signaling pathways including auxin, gib-berellin and cytokinin brassinolide ethylene and cytokinin-related genes were involved in the differentially growth between the upper and lower parts of rice shoot bases, and so do cell wall-related genes. Topological analysis of the coexpression networks revealed the core statue of AY177699.1(apetala3-like protein) and AK105103.1 at 0.5 h; AK062612.1 (ethylene response factor) and AK099932.1 (lectin-like receptor kinase 72) at 6 h. All the core factors have the function "response to endogenous stimulus". Additionally, AK108057.1(similar to germin-like protein precursor) was discovered as the most important core gene in the upper shoot bases in 6h after gravistimualtion while AK067424.1(cellulose synthase-like protein), AK120101.1 (Zinc finger, B-box domain containing protein) and CR278698 (ATPase associated with various cel-lular activities cellulose synthase-like protein) contribute equally to gravitropic response in the lower shoot bases.

  5. Characterization, Expression and Function of DORMANCY ASSOCIATED MADS-BOX Genes from Leafy Spurge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DORMANCY ASSOCIATED MADS-BOX (DAM) genes are related to AGAMOUS-LIKE 24 and SHORT VEGETATIVE PHASE genes of arabidopsis and are differentially regulated coordinately with endodormancy induction and release in buds of several perennial plant species. DAM genes were first shown to directly impact endo...

  6. Functional evolution of duplicated odorant-binding protein genes, Obp57d and Obp57e, in Drosophila.

    PubMed

    Harada, Eriko; Nakagawa, Jun; Asano, Tsunaki; Taoka, Masato; Sorimachi