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Classification of Biological Effect of 1,763 MHz Radiofrequency Radiation Based on Gene Expression Profiles.

Chang Nim IM ; Eun Hye KIM ; Ae Kyung PARK ; Woong Yang PARK

Genomics & Informatics.2010;8(1):34-40.

Radiofrequency (RF) radiation might induce the transcription of a certain set of genes as other physical stresses like ionizing radiation and UV. To observe transcriptional changes upon RF radiation, we exposed WI-38, human lung fibroblast cell to 1763 MHz of mobile phone RF radiation at 60 W/kg of specific absorption rate (SAR) for 24h with or without heat control. There were no significant changes in cell numbers and morphology after exposure to RF radiation. Using quantitative RT-PCR, we checked the expression of three heat shock protein (HSP) (HSPA1A, HSPA6 and HSP105) and seven stress-related genes (TNFRSF11B, FGF2, TGFB2, ITGA2, BRIP1, EXO1, and MCM10) in RF only and RF/HS groups of RF-exposed cells. The expressions of three heat shock proteins and seven stress-related genes were selectively changed only in RF/HS groups. Based on the expression of ten genes, we could classify thermal and non-thermal effect of RF-exposure, which genes can be used as biomarkers for RF radiation exposure.
Absorption ; Cell Count ; Cellular Phone ; Fibroblast Growth Factor 2 ; Fibroblasts ; Gene Expression ; Heat-Shock Proteins ; Hot Temperature ; Humans ; Lung ; Radiation, Ionizing ; Transcriptome ; Biomarkers

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Genome-wide Response of Normal WI-38 Human Fibroblast Cells to 1,763 MHz Radiofrequency Radiation.

Chang Nim IM ; Eun Hye KIM ; Ae Kyung PARK ; Woong Yang PARK

Genomics & Informatics.2010;8(1):28-33.

Increased exposure of human to RF fields has raised concerns for its potential adverse effects on our health. To address the biological effects of RF radiation, we used genome wide gene expression as the indicator. We exposed normal WI-38 human fibroblast cells to 1763 MHz mobile phone RF radiation at a specific absorption rate (SAR) of 60 W/kg with an operating cooling system for 24 h. There were no alterations in cell numbers or morphology after RF exposure. Through microarray analysis, we identified no differentially expressed genes (DEGs) at the 0.05 significance level after controlling for multiple testing errors with the Benjaminiochberg false discovery rate (BH FDR) method. Meanwhile, 82 genes were differentially expressed between RF-exposed cells and controls when the significance level was set at 0.01 without correction for multiple comparisons. We found that 24 genes (0.08% of the total genes examined) were changed by more than 1.5-fold on RF exposure. However, significant enrichment of any gene set or pathway was not observed from the functional annotation analysis. From these results, we did not find any evidence that non-thermal RF radiation at a 60-W/kg SAR significantly affects cell proliferation or gene expression in WI-38 cells.
Absorption ; Cell Count ; Cell Proliferation ; Cellular Phone ; Fibroblasts ; Gene Expression ; Genome ; Humans ; Microarray Analysis

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Replication of the Association between Copy Number Variation on 8p23.1 and Autism by Using ASD-specific BAC Array.

Jung Hoon WOO ; Song Ju YANG ; Seon Hee YIM ; Hae Jin HU ; Myung Ju SHIN ; Eun Hee OH ; Hyun Woong KANG ; Seonyang PARK ; Yeun Jun CHUNG

Genomics & Informatics.2010;8(1):19-27.

To discover genetic markers for autism spectrum disorder (ASD), we previously applied genome-wide BAC array comparative genomic hybridization (array-CGH) to 28 autistic patients and 62 normal controls in Korean population, and identified that chromosomal losses on 8p23.1 and on 17p11.2 are significantly associated with autism. In this study, we developed an 8.5K ASD-specific BAC array covering 27 previously reported ASD-associated CNV loci including ours and examined whether the associations would be replicated in 8 ASD patient cell lines of four different ethnic groups and 10 Korean normal controls. As a result, a CNV-loss on 8p23.1 was found to be significantly more frequent in patients regardless of ethnicity (p<0.0001). This CNV region contains two coding genes, DEFA1 and DEFA3, which are members of DEFENSIN gene family. Two other CNVs on 17p11.2 and Xp22.31 were also distributed differently between ASDs and controls, but not significant (p=0.069 and 0.092, respectively). All the other loci did not show significant association. When these evidences are considered, the association between ASD and CNV of DEFENSIN gene seems worthy of further exploration to elucidate the pathogenesis of ASD. Validation studies with a larger sample size will be required to verify its biological implication.
Autistic Disorder ; Cell Line ; Child ; Clinical Coding ; Coat Protein Complex I ; Comparative Genomic Hybridization ; Ethnic Groups ; Genetic Markers ; Humans ; Sample Size ; Autism Spectrum Disorder

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Putative Association of ITGB1 Haplotype with the Clearance of HBV Infection.

Tae Joon PARK ; Ji Yong CHUN ; Joon Seol BAE ; Jason Y KIM ; Jin Sol LEE ; Charisse Flerida PASAJE ; Byung Lae PARK ; Hyun Sub CHEONG ; Hyo Suk LEE ; Yoon Jun KIM ; Hyoung Doo SHIN

Genomics & Informatics.2010;8(1):9-18.

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (beta1) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and P(corr)=0.05). The minor allele frequency (MAF) of ITGB1 haplotype-2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.
Carcinoma, Hepatocellular ; Gene Frequency ; Haplotypes ; Humans ; Integrins ; Linkage Disequilibrium ; Liver ; Logistic Models ; Neoplasm Metastasis ; Proportional Hazards Models ; Proteins ; Sequence Analysis, DNA

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Association Analysis of SERPINB5 Polymorphisms with HBV Clearance and HCC Occurrence in a Korean Population.

Jason Y KIM ; Tae Joon PARK ; Jin Sol LEE ; Ji Yong CHUN ; Joon Seol BAE ; Byung Lae PARK ; Hyun Sub CHEONG ; Hyo Suk LEE ; Yoon Jun KIM ; Hyoung Doo SHIN

Genomics & Informatics.2010;8(1):1-8.

Serpin peptidase inhibitor, Clade B (ovalbumin), Member 5 (SERPINB5), also known as maspin, is a potent tumor suppressor gene. It has correlations with many tumor cells, from pancreas cancer to breast cancer, so it is possible that it may also affect liver cancer. There has also been a report that SERPINB12, a gene placed right next to SERPINB5, is expressed in liver. For this study, 32 polymorphisms were identified in SERPINB5 by direct DNA sequencing, and 11 of them were selected to be tested with a larger scale subjects. The association of the 11 SERPINB5 polymorphisms with Hepatitis B virus (HBV) clearance, hepatocellular carcinoma (HCC) occurrence and the onset age of HCC were analyzed. There were no significant associations found between 11 SERPINB5 polymorphisms and HBV clearance. In the case of HCC occurrence, one of the haplotypes (ht) showed association with HCC occurrence (OR=2.26, p=0.005, P(Cor)=0.05), albeit with a low statistical power (40.8%) and haplotype frequency (0.052). Further study with a bigger sample size will be needed to clearly verify the association between ht5 and HCC occurrence.
Age of Onset ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Genes, Tumor Suppressor ; Genes, vif ; Haplotypes ; Hepatitis B virus ; Liver ; Liver Neoplasms ; Pancreatic Neoplasms ; Sample Size ; Sequence Analysis, DNA ; Serpins

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Comparative Modeling and Molecular Dynamics Simulation of Substrate Binding in Human Fatty Acid Synthase: Enoyl Reductase and beta-Ketoacyl Reductase Catalytic Domains.

Arun JOHN ; Vetrivel UMASHANKAR ; Subramanian KRISHNAKUMAR ; Perinkulam Ravi DEEPA

Genomics & Informatics.2015;13(1):15-24. doi:10.5808/GI.2015.13.1.15

Fatty acid synthase (FASN, EC 2.3.1.85), is a multi-enzyme dimer complex that plays a critical role in lipogenesis. This lipogenic enzyme has gained importance beyond its physiological role due to its implications in several clinical conditions-cancers, obesity, and diabetes. This has made FASN an attractive pharmacological target. Here, we have attempted to predict the theoretical models for the human enoyl reductase (ER) and beta-ketoacyl reductase (KR) domains based on the porcine FASN crystal structure, which was the structurally closest template available at the time of this study. Comparative modeling methods were used for studying the structure-function relationships. Different validation studies revealed the predicted structures to be highly plausible. The respective substrates of ER and KR domains-namely, trans-butenoyl and beta-ketobutyryl-were computationally docked into active sites using Glide in order to understand the probable binding mode. The molecular dynamics simulations of the apo and holo states of ER and KR showed stable backbone root mean square deviation trajectories with minimal deviation. Ramachandran plot analysis showed 96.0% of residues in the most favorable region for ER and 90.3% for the KR domain, respectively. Thus, the predicted models yielded significant insights into the substrate binding modes of the ER and KR catalytic domains and will aid in identifying novel chemical inhibitors of human FASN that target these domains.
Catalytic Domain* ; Humans ; Lipogenesis ; Models, Theoretical ; Molecular Dynamics Simulation* ; Obesity ; Oxidoreductases*

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An Ontology-Based GIS for Genomic Data Management of Rumen Microbes.

Saber JELOKHANI-NIARAKI ; Mojtaba TAHMOORESPUR ; Zarrin MINUCHEHR ; Mohammad Reza NASSIRI

Genomics & Informatics.2015;13(1):7-14. doi:10.5808/GI.2015.13.1.7

During recent years, there has been exponential growth in biological information. With the emergence of large datasets in biology, life scientists are encountering bottlenecks in handling the biological data. This study presents an integrated geographic information system (GIS)-ontology application for handling microbial genome data. The application uses a linear referencing technique as one of the GIS functionalities to represent genes as linear events on the genome layer, where users can define/change the attributes of genes in an event table and interactively see the gene events on a genome layer. Our application adopted ontology to portray and store genomic data in a semantic framework, which facilitates data-sharing among biology domains, applications, and experts. The application was developed in two steps. In the first step, the genome annotated data were prepared and stored in a MySQL database. The second step involved the connection of the database to both ArcGIS and Protege as the GIS engine and ontology platform, respectively. We have designed this application specifically to manage the genome-annotated data of rumen microbial populations. Such a GIS-ontology application offers powerful capabilities for visualizing, managing, reusing, sharing, and querying genome-related data.
Biology ; Dataset ; Gene Ontology ; Genome ; Genome, Microbial ; Geographic Information Systems ; Rumen* ; Semantics

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Genes Involved in the Biosynthesis and Transport of Acinetobactin in Acinetobacter baumannii.

Tarik HASAN ; Chul Hee CHOI ; Man Hwan OH

Genomics & Informatics.2015;13(1):2-6. doi:10.5808/GI.2015.13.1.2

Pathogenic bacteria survive in iron-limited host environments by using several iron acquisition mechanisms. Acinetobacter baumannii, causing serious infections in compromised patients, produces an iron-chelating molecule, called acinetobactin, which is composed of equimolar quantities of 2,3-dihydroxybenzoic acid (DHBA), L-threonine, and N-hydroxyhistamine, to compete with host cells for iron. Genes that are involved in the production and transport of acinetobactin are clustered within the genome of A. baumannii. A recent study showed that entA, located outside of the acinetobactin gene cluster, plays important roles in the biosynthesis of the acinetobactin precursor DHBA and in bacterial pathogenesis. Therefore, understanding the genes that are associated with the biosynthesis and transport of acinetobactin in the bacterial genome is required. This review is intended to provide a general overview of the genes in the genome of A. baumannii that are required for acinetobactin biosynthesis and transport.
Acinetobacter baumannii* ; Bacteria ; Genome ; Genome, Bacterial ; Humans ; Iron ; Multigene Family ; Siderophores ; Threonine

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Editor's Introduction to This Issue.

Yeun Jun CHUNG

Genomics & Informatics.2015;13(1):1-1. doi:10.5808/GI.2015.13.1.1

No abstract available.

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Specificity of Intracellular Trans-Splicing Reaction by hTERT-Targeting Group I Intron.

Heung Su JUNG ; Byung Su KWON ; Seong Wook LEE

Genomics & Informatics.2005;3(4):172-174.

Recent anti-cancer approaches have been based to target tumor-specifically associated and/or causative molecules such as RNAs or proteins. As this specifically targeted anti-cancer modulator, we have previously described a novel human cancer gene therapeutic agent that is Tetrahymena group I intron-based trans-splicing ribozyme which can reprogram and replace human telomerase reverse transcriptase (hTERT) RNA to selectively induce tumor-specific cytotoxicity in cancer cells expressing the target RNA. Moreover, the specific ribozyme has been shown to efficiently retard tumor tissues in xenograft mice which had been inoculated with hTERT-expressing human cancer cells. In this study, we assessed specificity of trans-splicing reaction in cells to evaluate the therapeutic feasibility of the specific ribozyme. In order to analyze the trans-spliced products by the specific ribozyme in hTERT-positive cells, RT, 5'-end RACE-PCR, and sequencing reactions of the spliced RNAs were employed. Then, whole analyzed products resulted from reactions only with the hTERT RNA. This study suggested that the developed ribozyme perform highly specific RNA replacement of the target RNA in cells, hence trans-splicing ribozyme will be one of specific agents for genetic approach to revert cancer.
Animals ; Genes, Neoplasm ; Heterografts ; Humans ; Introns* ; Mice ; RNA ; Sensitivity and Specificity* ; Telomerase ; Tetrahymena ; Trans-Splicing*

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