International Journal of Genomics http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene Thu, 17 Apr 2014 12:08:07 +0000 http://www.hindawi.com/journals/ijg/2014/950903/ Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment. Qingqing Jiao, Cuiping Liu, Ziliang Yang, Qiang Ding, Miaomiao Wang, Min Li, Tingting Zhu, Hua Qian, Wei Li, Na Tu, Fumin Fang, Licai Ye, Zuotao Zhao, and Qihong Qian Copyright © 2014 Qingqing Jiao et al. All rights reserved. Microarray Analysis of the Juvenile Hormone Response in Larval Integument of the Silkworm, Bombyx mori Sun, 06 Apr 2014 06:49:12 +0000 http://www.hindawi.com/journals/ijg/2014/426025/ Juvenile hormone (JH) coordinates with 20-hydroxyecdysone (20E) to regulate larval growth and molting in insects. However, little is known about how this cooperative control is achieved during larval stages. Here, we induced silkworm superlarvae by applying the JH analogue (JHA) methoprene and used a microarray approach to survey the mRNA expression changes in response to JHA in the silkworm integument. We found that JHA application significantly increased the expression levels of most genes involved in basic metabolic processes and protein processing and decreased the expression of genes associated with oxidative phosphorylation in the integument. Several key genes involved in the pathways of insulin/insulin-like growth factor signaling (IIS) and 20E signaling were also upregulated after JHA application. Taken together, we suggest that JH may mediate the nutrient-dependent IIS pathway by regulating various metabolic pathways and further modulate 20E signaling. Daojun Cheng, Jian Peng, Meng Meng, Ling Wei, Lixia Kang, Wenliang Qian, and Qingyou Xia Copyright © 2014 Daojun Cheng et al. All rights reserved. Mechanism of Salinity Tolerance in Plants: Physiological, Biochemical, and Molecular Characterization Thu, 03 Apr 2014 12:32:37 +0000 http://www.hindawi.com/journals/ijg/2014/701596/ Salinity is a major abiotic stress limiting growth and productivity of plants in many areas of the world due to increasing use of poor quality of water for irrigation and soil salinization. Plant adaptation or tolerance to salinity stress involves complex physiological traits, metabolic pathways, and molecular or gene networks. A comprehensive understanding on how plants respond to salinity stress at different levels and an integrated approach of combining molecular tools with physiological and biochemical techniques are imperative for the development of salt-tolerant varieties of plants in salt-affected areas. Recent research has identified various adaptive responses to salinity stress at molecular, cellular, metabolic, and physiological levels, although mechanisms underlying salinity tolerance are far from being completely understood. This paper provides a comprehensive review of major research advances on biochemical, physiological, and molecular mechanisms regulating plant adaptation and tolerance to salinity stress. Bhaskar Gupta and Bingru Huang Copyright © 2014 Bhaskar Gupta and Bingru Huang. All rights reserved. A Promoter Region Polymorphism in PDCD-1 Gene Is Associated with Risk of Rheumatoid Arthritis in the Han Chinese Population of Southeastern China Thu, 03 Apr 2014 09:03:11 +0000 http://www.hindawi.com/journals/ijg/2014/247637/ Objective. Programmed cell death 1 (PD-1) induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of autoimmune diseases such as rheumatoid arthritis (RA). Herein, we investigate the association of PDCD-1 polymorphisms with the risk of RA among Chinese patients and healthy controls. Methods. Using the PCR-direct sequencing analysis, 4 PDCD-1 SNPs (rs36084323, rs11568821, rs2227982, and rs2227981) were genotyped in 320 RA patients and 309 matched healthy controls. Expression of PD-1 was determined in peripheral blood lymphocytes by flow cytometry and quantitative real-time reverse transcriptase polymerase chain reaction. Results. We observed that the GG genotype of rs36084323 was associated with a increased risk for developing RA (OR 1.70, 95% 1.11–2.61, ). Patients carrying G/G genotype displayed an increased mRNA level of PD-1 compared with A/A genotype and healthy controls. Meanwhile, patients homozygous for rs36084323 had induced basal PD-1 expression on activated CD4+ T cells. Conclusion. The PDCD-1 polymorphism rs36084323 was significantly associated with RA risk in Han Chinese population. This SNP, which effectively influenced the expression of PD-1, may be a biomarker of early diagnosis of RA and a suitable indicator of utilizing PD-1 inhibitor for treatment of RA. CuiPing Liu, JueAn Jiang, Li Gao, XiaoHan Hu, FengMing Wang, Yu Shen, GeHua Yu, ZuoTao Zhao, and XueGuang Zhang Copyright © 2014 CuiPing Liu et al. All rights reserved. Expression Data Analysis to Identify Biomarkers Associated with Asthma in Children Thu, 27 Mar 2014 09:40:08 +0000 http://www.hindawi.com/journals/ijg/2014/165175/ Asthma is characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing. It is usually caused by a combination of complex and incompletely understood environmental and genetic interactions. We obtained gene expression data with high-throughput screening and identified biomarkers of children's asthma using bioinformatics tools. Next, we explained the pathogenesis of children's asthma from the perspective of gene regulatory networks: DAVID was applied to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enriching analysis for the top 3000 pairs of relationships in differentially regulatory network. Finally, we found that HAND1, PTK1, NFKB1, ZIC3, STAT6, E2F1, PELP1, USF2, and CBFB may play important roles in children's asthma initiation. On account of regulatory impact factor (RIF) score, HAND1, PTK7, and ZIC3 were the potential asthma-related factors. Our study provided some foundations of a strategy for biomarker discovery despite a poor understanding of the mechanisms underlying children's asthma. Wen Xu Copyright © 2014 Wen Xu. All rights reserved. The WRKY Transcription Factor Genes in Lotus japonicus Sun, 16 Mar 2014 13:03:59 +0000 http://www.hindawi.com/journals/ijg/2014/420128/ WRKY transcription factor genes play critical roles in plant growth and development, as well as stress responses. WRKY genes have been examined in various higher plants, but they have not been characterized in Lotus japonicus. The recent release of the L. japonicus whole genome sequence provides an opportunity for a genome wide analysis of WRKY genes in this species. In this study, we identified 61 WRKY genes in the L. japonicus genome. Based on the WRKY protein structure, L. japonicus WRKY (LjWRKY) genes can be classified into three groups (I–III). Investigations of gene copy number and gene clusters indicate that only one gene duplication event occurred on chromosome 4 and no clustered genes were detected on chromosomes 3 or 6. Researchers previously believed that group II and III WRKY domains were derived from the C-terminal WRKY domain of group I. Our results suggest that some WRKY genes in group II originated from the N-terminal domain of group I WRKY genes. Additional evidence to support this hypothesis was obtained by Medicago truncatula WRKY (MtWRKY) protein motif analysis. We found that LjWRKY and MtWRKY group III genes are under purifying selection, suggesting that WRKY genes will become increasingly structured and functionally conserved. Hui Song, Pengfei Wang, Zhibiao Nan, and Xingjun Wang Copyright © 2014 Hui Song et al. All rights reserved. MicroRNAs in the Neural Retina Wed, 05 Mar 2014 15:39:38 +0000 http://www.hindawi.com/journals/ijg/2014/165897/ The health and function of the visual system rely on a collaborative interaction between diverse classes of molecular regulators. One of these classes consists of transcription factors, which are known to bind to DNA and control the transcription activities of their target genes. For a long time, it was thought that the transcription factors were the only regulators of gene expression. More recently, however, a novel class of regulators emerged. This class consists of a large number of small noncoding endogenous RNAs, namely, miRNAs. The miRNAs compose an essential component of posttranscriptional gene regulation, since they ultimately control the fate of gene transcripts. The retina, as a part of the central nervous system, is a well-established model for unraveling the molecular mechanisms underlying neuronal and glial functions. Numerous recent efforts have been made towards identification of miRNAs and their inferred roles in the visual pathway. In this review, we summarize the current state of our knowledge regarding the expression and function of miRNA in the neural retina and we discuss their potential uses as biomarkers for some retinal disorders. Kalina Andreeva and Nigel G. F. Cooper Copyright © 2014 Kalina Andreeva and Nigel G. F. Cooper. All rights reserved. Molecular Evolution of the Vertebrate FK506 Binding Protein 25 Sun, 02 Mar 2014 13:05:26 +0000 http://www.hindawi.com/journals/ijg/2014/402603/ FK506 binding proteins (FKBPs) belong to immunophilins with peptidyl-prolyl isomerases (PPIases) activity. FKBP25 (also known as FKBP3) is one of the nuclear DNA-binding proteins in the FKBPs family, which plays an important role in regulating transcription and chromatin structure. The calculation of nonsynonymous and synonymous substitution rates suggested that FKBP25 undergoes purifying selection throughout the whole vertebrate evolution. Moreover, the result of site-specific tests showed that no sites were detected under positive selection. Only one PPIase domain was detected by searching FKBP25 sequences at Pfam and SMART domain databases. Mammalian FKBP25 possess exon-intron conservation, although conservation in the whole vertebrate lineage is incomplete. The result of this study suggests that the purifying selection triggers FKBP25 evolutionary history, which allows us to discover the complete role of the PPIase domain in the interaction between FKBP25 and nuclear proteins. Moreover, intron alterations during FKBP25 evolution that regulate gene splicing may be involved in the purifying selection. Fei Liu, Xiao-Long Wei, Hao Li, Ji-Fu Wei, Yong-Qing Wang, and Xiao-Jian Gong Copyright © 2014 Fei Liu et al. All rights reserved. MicroRNAs in the DNA Damage/Repair Network and Cancer Thu, 30 Jan 2014 11:32:08 +0000 http://www.hindawi.com/journals/ijg/2014/820248/ Cancer is a multistep process characterized by various and different genetic lesions which cause the transformation of normal cells into tumor cells. To preserve the genomic integrity, eukaryotic cells need a complex DNA damage/repair response network of signaling pathways, involving many proteins, able to induce cell cycle arrest, apoptosis, or DNA repair. Chemotherapy and/or radiation therapy are the most commonly used therapeutic approaches to manage cancer and act mainly through the induction of DNA damage. Impairment in the DNA repair proteins, which physiologically protect cells from persistent DNA injury, can affect the efficacy of cancer therapies. Recently, increasing evidence has suggested that microRNAs take actively part in the regulation of the DNA damage/repair network. MicroRNAs are endogenous short noncoding molecules able to regulate gene expression at the post-transcriptional level. Due to their activity, microRNAs play a role in many fundamental physiological and pathological processes. In this review we report and discuss the role of microRNAs in the DNA damage/repair and cancer. Alessandra Tessitore, Germana Cicciarelli, Filippo Del Vecchio, Agata Gaggiano, Daniela Verzella, Mariafausta Fischietti, Davide Vecchiotti, Daria Capece, Francesca Zazzeroni, and Edoardo Alesse Copyright © 2014 Alessandra Tessitore et al. All rights reserved. Characterization of Genes for Beef Marbling Based on Applying Gene Coexpression Network Thu, 30 Jan 2014 09:59:47 +0000 http://www.hindawi.com/journals/ijg/2014/708562/ Marbling is an important trait in characterization beef quality and a major factor for determining the price of beef in the Korean beef market. In particular, marbling is a complex trait and needs a system-level approach for identifying candidate genes related to the trait. To find the candidate gene associated with marbling, we used a weighted gene coexpression network analysis from the expression value of bovine genes. Hub genes were identified; they were topologically centered with large degree and BC values in the global network. We performed gene expression analysis to detect candidate genes in M. longissimus with divergent marbling phenotype (marbling scores 2 to 7) using qRT-PCR. The results demonstrate that transmembrane protein 60 (TMEM60) and dihydropyrimidine dehydrogenase (DPYD) are associated with increasing marbling fat. We suggest that the network-based approach in livestock may be an important method for analyzing the complex effects of candidate genes associated with complex traits like marbling or tenderness. Dajeong Lim, Nam-Kuk Kim, Seung-Hwan Lee, Hye-Sun Park, Yong-Min Cho, Han-Ha Chai, and Heebal Kim Copyright © 2014 Dajeong Lim et al. All rights reserved. Dynamic Metabolic Footprinting Reveals the Key Components of Metabolic Network in Yeast Saccharomyces cerevisiae Wed, 29 Jan 2014 00:00:00 +0000 http://www.hindawi.com/journals/ijg/2014/894296/ Metabolic footprinting offers a relatively easy approach to exploit the potentials of metabolomics for phenotypic characterization of microbial cells. To capture the highly dynamic nature of metabolites, we propose the use of dynamic metabolic footprinting instead of the traditional method which relies on analysis at a single time point. Using direct infusion-mass spectrometry (DI-MS), we could observe the dynamic metabolic footprinting in yeast S. cerevisiae BY4709 (wild type) cultured on 3 different C-sources (glucose, glycerol, and ethanol) and sampled along 10 time points with 5 biological replicates. In order to analyze the dynamic mass spectrometry data, we developed the novel analysis methods that allow us to perform correlation analysis to identify metabolites that significantly correlate over time during growth on the different carbon sources. Both positive and negative electrospray ionization (ESI) modes were performed to obtain the complete information about the metabolite content. Using sparse principal component analysis (Sparse PCA), we further identified those pairs of metabolites that significantly contribute to the separation. From the list of significant metabolite pairs, we reconstructed an interaction map that provides information of how different metabolic pathways have correlated patterns during growth on the different carbon sources. Pramote Chumnanpuen, Michael Adsetts Edberg Hansen, Jørn Smedsgaard, and Jens Nielsen Copyright © 2014 Pramote Chumnanpuen et al. All rights reserved. Functional Expression Study of Igf2 Antisense Transcript in Mouse Thu, 16 Jan 2014 07:43:37 +0000 http://www.hindawi.com/journals/ijg/2014/390296/ Insulin-like growth factor antisense gene (Igf2as) expression was investigated in different mouse tissues during development, in differentiating C2C12 cells and in a DMR1-U2 knockout mouse model. The expression levels of Igf2as were high in fetal and newborn liver and muscle tissues compared to adults. The Igf2as gene was also expressed in placenta and in brain. The expression data suggests that the Igf2as gene plays a role in early development of the mouse and in placenta. There was no consistent evidence for an interaction between Igf2 and Igf2as transcripts. Furthermore, in knockout placentas lacking Igf2as transcription, Igf2 expression was comparable to that in wild type. These results indicate that Igf2as does not regulate Igf2 sense transcripts. In previous studies, it was suggested that the DMR1-U2 knockout mouse showing intrauterine growth restriction was caused by the absence of placenta-specific Igf2 P0 transcription. We conclude that the DMR1-U2 deletion phenotype should be reconsidered in the light of a functional Igf2as gene. Carolina Duart-Garcia and Martin H. Braunschweig Copyright © 2014 Carolina Duart-Garcia and Martin H. Braunschweig. All rights reserved. γ-H2AX: A Novel Prognostic Marker in a Prognosis Prediction Model of Patients with Early Operable Non-Small Cell Lung Cancer Wed, 08 Jan 2014 13:23:26 +0000 http://www.hindawi.com/journals/ijg/2014/160236/ Cancer is a leading cause of death worldwide and the prognostic evaluation of cancer patients is of great importance in medical care. The use of artificial neural networks in prediction problems is well established in human medical literature. The aim of the current study was to assess the prognostic value of a series of clinical and molecular variables with the addition of γ-H2AX—a new DNA damage response marker—for the prediction of prognosis in patients with early operable non-small cell lung cancer by comparing the γ-H2AX-based artificial network prediction model with the corresponding LR one. Two prognostic models of 96 patients with 27 input variables were constructed by using the parameter-increasing method in order to compare the predictive accuracy of neural network and logistic regression models. The quality of the models was evaluated by an independent validation data set of 11 patients. Neural networks outperformed logistic regression in predicting the patient’s outcome according to the experimental results. To assess the importance of the two factors p53 and γ-H2AX, models without these two variables were also constructed. JR and accuracy of these models were lower than those of the models using all input variables, suggesting that these biological markers are very important for optimal performance of the models. This study indicates that neural networks may represent a potentially more useful decision support tool than conventional statistical methods for predicting the outcome of patients with non-small cell lung cancer and that some molecular markers, such as γ-H2AX, enhance their predictive ability. E. Chatzimichail, D. Matthaios, D. Bouros, P. Karakitsos, K. Romanidis, S. Kakolyris, G. Papashinopoulos, and A. Rigas Copyright © 2014 E. Chatzimichail et al. All rights reserved. GOLink: Finding Cooccurring Terms across Gene Ontology Namespaces Tue, 31 Dec 2013 15:42:08 +0000 http://www.hindawi.com/journals/ijg/2013/594528/ The Gene Ontology (GO) provides a resource for consistent annotation of genes and gene products that is extensively used by numerous large public repositories. The GO is constructed of three subontologies describing the cellular component of action, molecular function, and overall biological process of a gene or gene product. Querying across the subontologies is problematic and no standard method exists to, for example, find all molecular functions occurring in a particular cellular component. GOLink addresses this problem by finding terms from all subontologies cooccurring with a term of interest in annotation across the entire GO database. Genes annotated with this term are exported and their GO annotation is assigned to three separate GOLink terms lists based on specific criteria. The software was used to predict the most likely Biological Process for a group of genes using just their Molecular Function terms giving sensitivity, specificity, and accuracy between 80 and 90% across all the terms lists. GOLink is made freely available for noncommercial use and can be downloaded from the project website. Richard W. Francis Copyright © 2013 Richard W. Francis. All rights reserved. A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk Tue, 31 Dec 2013 15:38:28 +0000 http://www.hindawi.com/journals/ijg/2013/406217/ A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure. Lewei Duan and Duncan C. Thomas Copyright © 2013 Lewei Duan and Duncan C. Thomas. All rights reserved. TSP-1-1223 A/G Polymorphism as a Potential Predictor of the Recurrence Risk of Bladder Cancer in a Chinese Population Tue, 03 Dec 2013 15:19:43 +0000 http://www.hindawi.com/journals/ijg/2013/473242/ Backgrounds. TSP-1 is a glycoprotein that functions in the biology of bladder cancer. We investigated the relationship between the distribution of TSP-1-1223 A/G polymorphism (rs2169830) and the clinical characteristics of bladder cancer. Materials and Methods. TaqMan assay was performed to determine the genotype of 609 cases and 670 control subjects in a Chinese population. Logistic regression was used to assess the association between the polymorphism and the risk of bladder cancer. Quantitative real-time polymerase chain reaction was performed to determine TSP-1 mRNA expression. Survival curves were generated using the Kaplan-Meier method. Results. No significant differences were detected in the genotype frequencies of healthy control subjects and patients with bladder cancer. By contrast, the time until the first recurrence differed significantly between genotypes (). The expression of TSP-1 mRNA in bladder cancer tissues was lower in patients with an AG genotype than in those with an AA genotype. The lowest expression was observed in patients with a GG genotype. Conclusions. In conclusion, TSP-1-1223 A/G polymorphism may contribute to the recurrence of bladder cancer in Chinese population. Xiao Yang, Pengchao Li, Xuejian Yang, Chao Qin, Qiang Cao, Zhengdong Zhang, Meilin Wang, Hongzhou Cai, Jinbao Gu, Jun Tao, Min Gu, Qiang Lu, and Changjun Yin Copyright © 2013 Xiao Yang et al. All rights reserved. Microarray Analysis of Transcriptome of Medulla Identifies Potential Biomarkers for Parkinson’s Disease Wed, 20 Nov 2013 11:10:58 +0000 http://www.hindawi.com/journals/ijg/2013/606919/ To complement the molecular pathways contributing to Parkinson’s disease (PD) and identify potential biomarkers, gene expression profiles of two regions of the medulla were compared between PD patients and control. GSE19587 containing two groups of gene expression profiles [6 dorsal motor nucleus of the vagus (DMNV) samples from PD patients and 5 from controls, 6 inferior olivary nucleus (ION) samples from PD patients and 5 from controls] was downloaded from Gene Expression Omnibus. As a result, a total of 1569 and 1647 differentially expressed genes (DEGs) were, respectively, screened in DMNV and ION with limma package of R. The functional enrichment analysis by DAVID server (the Database for Annotation, Visualization and Integrated Discovery) indicated that the above DEGs may be involved in the following processes, such as regulation of cell proliferation, positive regulation of macromolecule metabolic process, and regulation of apoptosis. Further analysis showed that there were 365 common DEGs presented in both regions (DMNV and ION), which may be further regulated by eight clusters of microRNAs retrieved with WebGestalt. The genes in the common DEGs-miRNAs regulatory network were enriched in regulation of apoptosis process via DAVID analysis. These findings could not only advance the understandings about the pathogenesis of PD, but also suggest potential biomarkers for this disease. Xiao-Yang Liao, Wei-Wen Wang, Zheng-Hui Yang, Jun Wang, Hang Lin, Qing-Song Wang, Yu-Xian Wu, and Yu Liu Copyright © 2013 Xiao-Yang Liao et al. All rights reserved. Differential Expression of Myogenic Regulatory Factor Genes in the Skeletal Muscles of Tambaqui Colossoma macropomum (Cuvier 1818) from Amazonian Black and Clear Water Tue, 19 Nov 2013 09:47:12 +0000 http://www.hindawi.com/journals/ijg/2013/465727/ Hypothesizing that the Amazonian water system differences would affect the expression of muscle growth-related genes in juvenile tambaqui Colossoma macropomum (Cuvier 1818), this study aimed to analyze the morphometric data and expression of myogenic regulatory factors (MRFs) in the white and red muscle from tambaqui obtained from clear and black Amazonian water systems. All of the MRF transcript levels (myod, myf5, myogenin, and mrf4) were significantly lower in the red muscle from black water fish in comparison to clear water fish. However, in white muscle, only the myod transcript level was significantly decreased in the black water tambaqui. The changes in MRFs gene expression in muscle fibers of tambaqui from black water system provide relevant information about the environmental influence as that of water systems on gene expression of muscle growth related genes in the C. macropomum. Our results showed that the physical and chemical water characteristics change the expression of genes that promote muscle growth, and these results may be also widely applicable to future projects that aim to enhance muscle growth in fish that are of substantial interest to the aquaculture. F. A. Alves-Costa, C. M. Barbosa, R. C. M. Aguiar, E. A. Mareco, and M. Dal-Pai-Silva Copyright © 2013 F. A. Alves-Costa et al. All rights reserved. Identification of Cassava MicroRNAs under Abiotic Stress Thu, 14 Nov 2013 14:03:14 +0000 http://www.hindawi.com/journals/ijg/2013/857986/ The study of microRNAs (miRNAs) in plants has gained significant attention in recent years due to their regulatory role during development and in response to biotic and abiotic stresses. Although cassava (Manihot esculenta Crantz) is tolerant to drought and other adverse conditions, most cassava miRNAs have been predicted using bioinformatics alone or through sequencing of plants challenged by biotic stress. Here, we use high-throughput sequencing and different bioinformatics methods to identify potential cassava miRNAs expressed in different tissues subject to heat and drought conditions. We identified 60 miRNAs conserved in other plant species and 821 potential cassava-specific miRNAs. We also predicted 134 and 1002 potential target genes for these two sets of sequences. Using real time PCR, we verified the condition-specific expression of 5 cassava small RNAs relative to a non-stress control. We also found, using publicly available expression data, a significantly lower expression of the predicted target genes of conserved and nonconserved miRNAs under drought stress compared to other cassava genes. Gene Ontology enrichment analysis along with condition specific expression of predicted miRNA targets, allowed us to identify several interesting miRNAs which may play a role in stress-induced posttranscriptional regulation in cassava and other plants. Carolina Ballén-Taborda, Germán Plata, Sarah Ayling, Fausto Rodríguez-Zapata, Luis Augusto Becerra Lopez-Lavalle, Jorge Duitama, and Joe Tohme Copyright © 2013 Carolina Ballén-Taborda et al. All rights reserved. Extracting Evolutionary Insights Using Bioinformatics Wed, 13 Nov 2013 10:35:34 +0000 http://www.hindawi.com/journals/ijg/2013/376235/ Dmitry Sherbakov, Yuri Panchin, and Ancha Baranova Copyright © 2013 Dmitry Sherbakov et al. All rights reserved. XRCC7 rs#7003908 Polymorphism and Helicobacter pylori Infection-Related Gastric Antrum Adenocarcinoma Mon, 11 Nov 2013 13:13:08 +0000 http://www.hindawi.com/journals/ijg/2013/124612/ The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03–8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89–22.77) for XRCC7-TG and 38.49 (22.82–64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA. Chao Wang, Xiao-Ying Huang, Jin-Guang Yao, Bing-Chen Huang, Cen-Han Huang, Pinhu Liao, and Xi-Dai Long Copyright © 2013 Chao Wang et al. All rights reserved. Association of Genetic Variation in Calmodulin and Left Ventricular Mass in Full-Term Newborns Tue, 05 Nov 2013 08:31:38 +0000 http://www.hindawi.com/journals/ijg/2013/410407/ Calmodulin II (CALM2) gene polymorphism might be responsible for the variation in the left ventricular mass amongst healthy individuals. The aim was to evaluate the correlation between left ventricular mass (LVM) and g.474955027G>A (rs7565161) polymorphism adjacent to the CALM2 gene. Healthy Polish newborns (n = 206) were recruited. Two-dimensional M-mode echocardiography was used to assess LVM. Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism and sequencing analyses. The carriers of the G allele of the CALM2 polymorphism had significantly higher left ventricular mass/weight (LVM/BW) values, when compared with newborns homozygous for the A allele (3.1 g/m2 versus 2.5 g/m2, = 0.036). The AG genotype of CALM2 was associated with the highest values of LVM/BW, exhibiting a pattern of overdominance (2.9 g/kg versus 3.1 g/kg versus 2.5 g/kg, = 0.037). The results of this study suggest that G>A CALM2 polymorphism may account for subtle variation in LVM at birth. Iwona Gorący, Jarosław Gorący, Karolina Skonieczna-Żydecka, Mariusz Kaczmarczyk, Grażyna Dawid, and Andrzej Ciechanowicz Copyright © 2013 Iwona Gorący et al. All rights reserved. Genome Stability Pathways in Head and Neck Cancers Mon, 04 Nov 2013 14:30:57 +0000 http://www.hindawi.com/journals/ijg/2013/464720/ Genomic instability underlies the transformation of host cells toward malignancy, promotes development of invasion and metastasis and shapes the response of established cancer to treatment. In this review, we discuss recent advances in our understanding of genomic stability in squamous cell carcinoma of the head and neck (HNSCC), with an emphasis on DNA repair pathways. HNSCC is characterized by distinct profiles in genome stability between similarly staged cancers that are reflected in risk, treatment response and outcomes. Defective DNA repair generates chromosomal derangement that can cause subsequent alterations in gene expression, and is a hallmark of progression toward carcinoma. Variable functionality of an increasing spectrum of repair gene polymorphisms is associated with increased cancer risk, while aetiological factors such as human papillomavirus, tobacco and alcohol induce significantly different behaviour in induced malignancy, underpinned by differences in genomic stability. Targeted inhibition of signalling receptors has proven to be a clinically-validated therapy, and protein expression of other DNA repair and signalling molecules associated with cancer behaviour could potentially provide a more refined clinical model for prognosis and treatment prediction. Development and expansion of current genomic stability models is furthering our understanding of HNSCC pathophysiology and uncovering new, promising treatment strategies. Glenn Jenkins, Kenneth J. O'Byrne, Benedict Panizza, and Derek J. Richard Copyright © 2013 Glenn Jenkins et al. All rights reserved. Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach Wed, 30 Oct 2013 10:10:55 +0000 http://www.hindawi.com/journals/ijg/2013/624681/ The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development. Maricela Rodríguez-Cruz, Ramón M. Coral-Vázquez, Gabriel Hernández-Stengele, Raúl Sánchez, Emmanuel Salazar, Fausto Sanchez-Muñoz, Sergio Encarnación-Guevara, and Jorge Ramírez-Salcedo Copyright © 2013 Maricela Rodríguez-Cruz et al. All rights reserved. Comparative Inference of Duplicated Genes Produced by Polyploidization in Soybean Genome Wed, 09 Oct 2013 12:49:54 +0000 http://www.hindawi.com/journals/ijg/2013/275616/ Soybean (Glycine max) is one of the most important crop plants for providing protein and oil. It is important to investigate soybean genome for its economic and scientific value. Polyploidy is a widespread and recursive phenomenon during plant evolution, and it could generate massive duplicated genes which is an important resource for genetic innovation. Improved sequence alignment criteria and statistical analysis are used to identify and characterize duplicated genes produced by polyploidization in soybean. Based on the collinearity method, duplicated genes by whole genome duplication account for 70.3% in soybean. From the statistical analysis of the molecular distances between duplicated genes, our study indicates that the whole genome duplication event occurred more than once in the genome evolution of soybean, which is often distributed near the ends of chromosomes. Yanmei Yang, Jinpeng Wang, and Jianyong Di Copyright © 2013 Yanmei Yang et al. All rights reserved. Integrated Analysis of Long Noncoding RNA and Coding RNA Expression in Esophageal Squamous Cell Carcinoma Mon, 07 Oct 2013 19:00:11 +0000 http://www.hindawi.com/journals/ijg/2013/480534/ Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the “cancer initiatome.” Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer. Wei Cao, Wei Wu, Fachun Shi, Xiaobing Chen, Lihua Wu, Ke Yang, Fu Tian, Minghui Zhu, Guoyong Chen, WeiWei Wang, Fred G. Biddle, and Jianqin Gu Copyright © 2013 Wei Cao et al. All rights reserved. Target Gene and Function Prediction of Differentially Expressed MicroRNAs in Lactating Mammary Glands of Dairy Goats Mon, 30 Sep 2013 13:27:05 +0000 http://www.hindawi.com/journals/ijg/2013/917342/ MicroRNAs are small noncoding RNAs that can regulate gene expression, and they can be involved in the regulation of mammary gland development. The differential expression of miRNAs during mammary gland development is expected to provide insight into their roles in regulating the homeostasis of mammary gland tissues. To screen out miRNAs that should have important regulatory function in the development of mammary gland from miRNA expression profiles and to predict their function, in this study, the target genes of differentially expressed miRNAs in the lactating mammary glands of Laoshan dairy goats are predicted, and then the functions of these miRNAs are analyzed via bioinformatics. First, we screen the expression patterns of 25 miRNAs that had shown significant differences during the different lactation stages in the mammary gland. Then, these miRNAs are clustered according to their expression patterns. Computational methods were used to obtain 215 target genes for 22 of these miRNAs. Combining gene ontology annotation, Fisher’s exact test, and KEGG analysis with the target prediction for these miRNAs, the regulatory functions of miRNAs belonging to different clusters are predicted. Fei Dong, Zhi-Bin Ji, Cun-Xian Chen, Gui-Zhi Wang, and Jian-Min Wang Copyright © 2013 Fei Dong et al. All rights reserved. Extensive Differences in Antifungal Immune Response in Two Drosophila Species Revealed by Comparative Transcriptome Analysis Tue, 10 Sep 2013 08:08:18 +0000 http://www.hindawi.com/journals/ijg/2013/542139/ The innate immune system of Drosophila is activated by ingestion of microorganisms. D. melanogaster breeds on fruits fermented by Saccharomyces cerevisiae, whereas D. virilis breeds on slime flux and decaying bark of tree housing a variety of bacteria, yeasts, and molds. In this study, it is shown that D. virilis has a higher resistance to oral infection of a species of filamentous fungi belonging to the genus Penicillium compared to D. melanogaster. In response to the fungal infection, a transcriptome profile of immune-related genes was considerably different between D. melanogaster and D. virilis: the genes encoding antifungal peptides, Drosomycin and Metchnikowin, were highly expressed in D. melanogaster whereas, the genes encoding Diptericin and Defensin were highly expressed in D. virilis. On the other hand, the immune-induced molecule (IM) genes showed contrary expression patterns between the two species: they were induced by the fungal infection in D. melanogaster but tended to be suppressed in D. virilis. Our transcriptome analysis also showed newly predicted immune-related genes in D. virilis. These results suggest that the innate immune system has been extensively differentiated during the evolution of these Drosophila species. Yosuke Seto and Koichiro Tamura Copyright © 2013 Yosuke Seto and Koichiro Tamura. All rights reserved. RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response Tue, 03 Sep 2013 09:15:48 +0000 http://www.hindawi.com/journals/ijg/2013/271347/ A proper DNA damage response (DDR), which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such as p21WAF1, BAX, and PUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage. Toshinori Ozaki, Akira Nakagawara, and Hiroki Nagase Copyright © 2013 Toshinori Ozaki et al. All rights reserved. Effects of Cortisol Administered through Slow-Release Implants on Innate Immune Responses in Rainbow Trout (Oncorhynchus mykiss) Thu, 29 Aug 2013 11:31:45 +0000 http://www.hindawi.com/journals/ijg/2013/619714/ Cortisol is a key hormone in the fish stress response with a well-known ability to regulate several physiological functions, including energy metabolism and the immune system. However, data concerning cortisol effects on fish innate immune system using a more controlled increase in cortisol levels isolated from any other stress related signaling is scarce. The present study describes the effect of doses of cortisol corresponding to acute and chronic levels on the complement and lysozyme activity in plasma of the rainbow trout (Oncorhynchus mykiss). We also evaluated the effects of these cortisol levels (from intraperitoneally implanted hydrocortisone) on the mRNA levels quantified by RT-qPCR of selected key immune-related genes in the liver, head kidney, and spleen. For that purpose, 60 specimens of rainbow trout were divided in to two groups: a control group injected with a coconut oil implant and another group injected with the same implant and cortisol (50 μg cortisol/g body weight). Our results demonstrate the role of cortisol as a modulator of the innate immune response without the direct contribution of other stress axes. Our results also show a relationship between the complement and lysozyme activity in plasma and mRNA levels in liver, supporting the important role of this organ in producing these immune system proteins after a rise of cortisol in the fish plasma. R. Cortés, M. Teles, R. Trídico, L. Acerete, and L. Tort Copyright © 2013 R. Cortés et al. All rights reserved.