International Journal of Genomics The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Drug-Related Genomics in Cancer and Immunological Diseases Wed, 23 Jul 2014 06:28:35 +0000 Ji-Fu Wei, Yong-Qing Wang, and Huai-Rong Luo Copyright © 2014 Ji-Fu Wei et al. All rights reserved. Compositional Constraint Is the Key Force in Shaping Codon Usage Bias in Hemagglutinin Gene in H1N1 Subtype of Influenza A Virus Thu, 17 Jul 2014 12:10:25 +0000 It is vital to unravel the codon usage bias in order to gain insights into the evolutionary forces dictating the viral evolution process. Influenza A virus has attracted attention of many investigators over the years due to high mutation rate and being cross-specific shift operational in the viral genome. Several authors have reported that the codon usage bias is low in influenza A viruses, citing mutational pressure as the decisive force shaping up the codon usage in these viruses. In this study, complete coding sequences of hemagglutinin genes for H1N1 subtype of influenza A virus have been explored for the possible codon usage bias acting upon these genes. The results indicate overall low bias with peaking ENC values. The GC content is found to be substantially low as against AT content in the silent codon sites. Significant correlations were observed in between the compositional parameters versus AT3, implying the possible role of the latter in shaping codon usage profile in the viral hemagglutinin. The data showed conspicuously that the sequences were A redundant with most codons preferring nucleotide A over others in the third synonymous codon site. The results indicated the pivotal role of compositional pressure affecting codon usage in this virus. Himangshu Deka and Supriyo Chakraborty Copyright © 2014 Himangshu Deka and Supriyo Chakraborty. All rights reserved. Comparative Analysis of Glycogene Expression in Different Mouse Tissues Using RNA-Seq Data Wed, 09 Jul 2014 14:17:28 +0000 Glycogenes regulate a wide array of biological processes in the development of organisms as well as different diseases such as cancer, primary open-angle glaucoma, and renal dysfunction. The objective of this study was to explore the role of differentially expressed glycogenes (DEGGs) in three major tissues such as brain, muscle, and liver using mouse RNA-seq data, and we identified 579, 501, and 442 DEGGs for brain versus liver (BvL579), brain versus muscle (BvM501), and liver versus muscle (LvM442) groups. DAVID functional analysis suggested inflammatory response, glycosaminoglycan metabolic process, and protein maturation as the enriched biological processes in BvL579, BvM501, and LvM442, respectively. These DEGGs were then used to construct three interaction networks by using GeneMANIA, from which we detected potential hub genes such as PEMT and HPXN (BvL579), IGF2 and NID2 (BvM501), and STAT6 and FLT1 (LvM442), having the highest degree. Additionally, our community analysis results suggest that the significance of immune system related processes in liver, glycosphingolipid metabolic processes in the development of brain, and the processes such as cell proliferation, adhesion, and growth are important for muscle development. Further studies are required to confirm the role of predicted hub genes as well as the significance of biological processes. Ahmad Firoz, Adeel Malik, Sanjay Kumar Singh, Vivekanand Jha, and Amjad Ali Copyright © 2014 Ahmad Firoz et al. All rights reserved. Associations of CTLA4 Gene Polymorphisms with Graves’ Ophthalmopathy: A Meta-Analysis Wed, 09 Jul 2014 06:40:59 +0000 Many studies have established that T-lymphocyte antigen-4 (CTLA4) is a susceptible gene for Graves’ disease (GD). Also many studies showed the association between the CTLA4 exon-1 49A/G polymorphism and the risk of developing Graves’ ophthalmopathy (GO) in GD patients. But those results were inconsistent. In recent years many new studies were published which helped to shed light on the relationship of CTLA4 SNP49 with GO. So we performed the meta-analysis to explore the association between the SNP49 and GO susceptibility in GD patients. Studies up to February 29, 2012, were searched by using PubMed. The odds ratio was used to evaluate the strength of the association. Altogether 12 case-control studies involving 2,505 participants were included in the meta-analysis. Results showed that the G allele was related to the increased risk of GO compared with the A allele under allelic genetic model (OR = 1.14, 95% CI: 1.14–1.72, ) in European subgroup. No publication bias was detected. Our results showed that the SNP49 polymorphism of CTLA4 gene was related to increased risk of GO. Pengfei Du, Xiaojie Ma, and Changjiang Wang Copyright © 2014 Pengfei Du et al. All rights reserved. Identification of Differentially Expressed Gene after Femoral Fracture via Microarray Profiling Tue, 08 Jul 2014 08:17:44 +0000 We aimed to investigate differentially expressed genes (DEGs) in different stages after femoral fracture based on rat models, providing the basis for the treatment of sport-related fractures. Gene expression data GSE3298 was downloaded from Gene Expression Omnibus (GEO), including 16 chips. All femoral fracture samples were classified into earlier fracture stage and later fracture stage. Total 87 DEGs simultaneously occurred in two stages, of which 4 genes showed opposite expression tendency. Out of the 4 genes, Rest and Cst8 were hub nodes in protein-protein interaction (PPI) network. The GO (Gene Ontology) function enrichment analysis verified that nutrition supply related genes were enriched in the earlier stage and neuron growth related genes were enriched in the later stage. Calcium signaling pathway was the most significant pathway in earlier stage; in later stage, DEGs were enriched into 2 neurodevelopment-related pathways. Analysis of Pearson's correlation coefficient showed that a total of 3,300 genes were significantly associated with fracture time, none of which was overlapped with identified DEGs. This study suggested that Rest and Cst8 might act as potential indicators for fracture healing. Calcium signaling pathway and neurodevelopment-related pathways might be deeply involved in bone healing after femoral fracture. Donggen Zhong Copyright © 2014 Donggen Zhong. All rights reserved. Coexpression within Integrated Mitochondrial Pathways Reveals Different Networks in Normal and Chemically Treated Transcriptomes Tue, 24 Jun 2014 12:06:20 +0000 As energy producers, mitochondria play a pivotal role in multiple cellular processes. Although several lines of evidence suggest that differential expression of mitochondrial respiratory complexes (MRCs) has a significant impact on mitochondrial function, the role of integrated MRCs in the whole coexpression network has yet to be revealed. In this study, we construct coexpression networks based on microarray datasets from different tissues and chemical treatments to explore the role of integrated MRCs in the coexpression network and the effects of different chemicals on the mitochondrial network. By grouping MRCs as one seed target, the hypergeometric distribution allowed us to identify genes that are significantly coexpress with whole MRCs. Coexpression among 46 MRC genes (approximately 78% of MRC genes tested) was significant in the normal tissue transcriptome dataset. These MRC genes are coexpressed with genes involved in the categories “muscle system process,” “metabolic process,” and “neurodegenerative disease pathways,” whereas, in the chemically treated tissues, coexpression of these genes mostly disappeared. These results indicate that chemical stimuli alter the normal coexpression network of MRC genes. Taken together, the datasets obtained from the different coexpression networks are informative about mitochondrial biogenesis and should contribute to understanding the side effects of drugs on mitochondrial function. Cong Chen, Tae Kyung Hyun, Xiao Han, Zhihui Feng, Yuan Li, Xiaolong Liu, and Jiankang Liu Copyright © 2014 Cong Chen et al. All rights reserved. High Expression of Polo-Like Kinase 1 Is Associated with Early Development of Hepatocellular Carcinoma Wed, 11 Jun 2014 11:59:55 +0000 Polo-like kinase 1 (PLK1), one of serine/threonine-protein kinase, has been demonstrated to play pivotal roles in malignant transformation. Here we illustrated the clinicopathological significance of PLK1 expression in hepatocellular carcinoma (HCC) in more detail. Immunohistochemistry was performed to detect the expression of PLK1 in 67 HCC patients as well as corresponding noncancerous liver tissues. In addition, the correlation of PLK1 expression with clinicopathological factors or prognosis of HCC was analyzed. Results showed that the expression of PLK1 was increased significantly in HCC tissues than that of corresponding normal liver tissues. The correlation between PLK1 and HCC cell differentiation or capsule invasion was also revealed. We found that PLK1 inhibition promoted cell arrest in G2/M phase of cell cycle and cell apoptosis. Our results also indicated that the potential mechanisms of PLK1 inhibition regulating cell growth involved enhancing expression of caspase3, caspase8, and Bax and decreasing expression of Bcl-2. Furthermore, we also found that PLK1 downregulation inducing inhibition of cell growth was associated with enhancing expression of p53. Thus, we presume that the status of PLK1 expression might be an independent prognostic factor for HCC and targeting PLK1 might be a useful strategy for diagnosis and treatment of human HCC. Wei Sun, Qi Su, Xiankui Cao, Bin Shang, Aishan Chen, Hongzhuan Yin, and Baolin Liu Copyright © 2014 Wei Sun et al. All rights reserved. Genetic Variations of Cytokines and Cytokine Receptors in Psoriasis Patients from China Sun, 25 May 2014 08:00:03 +0000 Psoriasis is a chronic inflammatory and hyperproliferative skin disease affected by both genetic and environmental factors. The aim of the present study was to investigate polymorphisms in a candidate gene family of interleukin (IL) in unrelated Chinese patients with psoriasis and control subjects without psoriasis. In this case-control study, 200 unrelated Chinese psoriasis patients and 298 age- and sex-matched control subjects were enrolled. Genomic DNA was prepared from peripheral blood obtained from all psoriasis patients and control subjects. We genotyped seven single-nucleotide polymorphisms (SNPs) in candidate genes of six ILs: IL4, IL10, IL12B, IL13, IL15, and IL23R, which have been shown in the literature to be associated with psoriasis in other ethnic groups. Among the seven SNPs in the six IL genes studied, only the rs3212227 in the IL12B gene was found to be associated with psoriasis at genotypic level in the studied population. The C/C genotype in the IL12B gene is a protective factor of psoriasis (; OR = 0.51; 95% CI: 0.27–0.96) in Chinese. Furthermore, the studied Chinese population has extremely low minor allele frequency for IL23R. Together, the data reveal unique genetic patterns in Chinese that may be in part responsible for the lower risk for psoriasis in this population. Xiao-Lan Li, Chun-Feng Wu, and Gui-Sheng Wu Copyright © 2014 Xiao-Lan Li et al. All rights reserved. In Silico Prediction of T and B Cell Epitopes of Der f 25 in Dermatophagoides farinae Thu, 08 May 2014 00:00:00 +0000 The house dust mites are major sources of indoor allergens for humans, which induce asthma, rhinitis, dermatitis, and other allergic diseases. Der f 25 is a triosephosphate isomerase, representing the major allergen identified in Dermatophagoides farinae. The objective of this study was to predict the B and T cell epitopes of Der f 25. In the present study, we analyzed the physiochemical properties, function motifs and domains, and structural-based detailed features of Der f 25 and predicted the B cell linear epitopes of Der f 25 by DNAStar protean system, BPAP, and BepiPred 1.0 server and the T cell epitopes by NetMHCIIpan-3.0 and NetMHCII-2.2. As a result, the sequence and structure analysis identified that Der f 25 belongs to the triosephosphate isomerase family and exhibited a triosephosphate isomerase pattern (PS001371). Eight B cell epitopes (11–18, 30–35, 71–77, 99–107, 132–138, 173–187, 193–197, and 211–224) and five T cell epitopes including 26–34, 38–54, 66–74, 142–151, and 239–247 were predicted in this study. These results can be used to benefit allergen immunotherapies and reduce the frequency of mite allergic reactions. Xiaohong Li, Hai-Wei Yang, Hao Chen, Jing Wu, Yehai Liu, and Ji-Fu Wei Copyright © 2014 Xiaohong Li et al. All rights reserved. Association between NFKB1 −94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis Wed, 07 May 2014 14:23:38 +0000 Nuclear factor-κB is associated with the pathogenesis of numerous malignancies, and the functional polymorphism −94ins/del ATTG (rs28362491) in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the −94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. We found that the NFKB1 promoter −94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11–1.93; dominant model, OR = 1.26, 95% CI = 1.03–1.53; recessive model, OR = 1.26, 95% CI = 1.05–1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05–1.35). Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect. Xiao Yang, Pengchao Li, Jun Tao, Chao Qin, Qiang Cao, Jinbao Gu, Xiaheng Deng, Jun Wang, Xuzhong Liu, Zijie Wang, Bian Wu, Min Gu, Qiang Lu, and Changjun Yin Copyright © 2014 Xiao Yang et al. All rights reserved. Identification and Expression Profiling of the BTB Domain-Containing Protein Gene Family in the Silkworm, Bombyx mori Tue, 06 May 2014 13:05:48 +0000 The BTB domain is a conserved protein-protein interaction motif. In this study, we identified 56 BTB domain-containing protein genes in the silkworm, in addition to 46 in the honey bee, 55 in the red flour beetle, and 53 in the monarch butterfly. Silkworm BTB protein genes were classified into nine subfamilies according to their domain architecture, and most of them could be mapped on the different chromosomes. Phylogenetic analysis suggests that silkworm BTB protein genes may have undergone a duplication event in three subfamilies: BTB-BACK-Kelch, BTB-BACK-PHR, and BTB-FLYWCH. Comparative analysis demonstrated that the orthologs of each of 13 BTB protein genes present a rigorous orthologous relationship in the silkworm and other surveyed insects, indicating conserved functions of these genes during insect evolution. Furthermore, several silkworm BTB protein genes exhibited sex-specific expression in larval tissues or at different stages during metamorphosis. These findings not only contribute to a better understanding of the evolution of insect BTB protein gene families but also provide a basis for further investigation of the functions of BTB protein genes in the silkworm. Daojun Cheng, Wenliang Qian, Meng Meng, Yonghu Wang, Jian Peng, and Qingyou Xia Copyright © 2014 Daojun Cheng et al. 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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.