• Asian-Australasian Journal of Animal Sciences
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• v.17 no.10
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• pp.1344-1349
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• 2004

Titin-cap (TCAP), one of the abundant transcripts in skeletal muscles, was nvestigated in this study in cattle because of its role in regulating the proliferation and differentiation of myoblasts by interacting with the myostatin gene. From the 5, and 3, RACE experiments, full-length TCAP coding sequence was identified, comprising 166 amino acids. The amino acid comparison showed high sequence similarities with previously identified human (95.8%) and mouse (95.2%) TCAP genes. The TCAP expression, addressed by northern blot, is limited in muscle tissues as indicated by Valle et al. (1997). The radiation hybrid analysis localized the gene on BTA19, where the comparative human and porcine counterparts are on HSA17 and SSC12. A few muscle-related genetic disorders were mapped on HSA17 and some growth-related QTLs were identified on SSC12. The bovine TCAP gene found in this study opens up new possibilities for the investigation of muscle-related genetic diseases as well as meat yield traits in cattle.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2000.11a
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• pp.56-58
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• 2000

Post-genomics may be defined in different ways depending on how one views the challenges after the genome. A popular view is to follow the concept of the central dogma in molecular biology, namely from genome to transcriptome to proteome. Projects are going on to analyze gene expression profiles both at the mRNA and protein levels and to catalog protein 3D structure families, which will no doubt help the understanding of information in the genome. However complete, such catalogs of genes, RNAs, and proteins only tell us about the building blocks of life. They do not tell us much about the wiring (interaction) of building blocks, which is essential for uncovering systemic functional behaviors of the cell or the organism. Thus, an alternative view of post-genomics is to go up from the molecular level to the cellular level, and to understand, what I call, the "interactome"or a complete picture of molecular interactions in the cell. KEGG (http://www.genome.ad.jp/kegg/) is our attempt to computerize current knowledge on various cellular processes as a collection of "generalized"protein-protein interaction networks, to develop new graph-based algorithms for predicting such networks from the genome information, and to actually reconstruct the interactomes for all the completely sequenced genomes and some partial genomes. During the reconstruction process, it becomes readily apparent that certain pathways and molecular complexes are present or absent in each organism, indicating modular structures of the interactome. In addition, the reconstruction uncovers missing components in an otherwise complete pathway or complex, which may result from misannotation of the genome or misrepresentation of the KEGG pathway. When combined with additional experimental data on protein-protein interactions, such as by yeast two-hybrid systems, the reconstruction possibly uncovers unknown partners for a particular pathway or complex. Thus, the reconstruction is tightly coupled with the annotation of individual genes, which is maintained in the GENES database in KEGG. We are also trying to expand our literature surrey to include in the GENES database most up-to-date information about gene functions.

• Genomics & Informatics
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• v.21 no.3
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• pp.32.1-32.11
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• 2023

Resistance to anti-tuberculosis drugs, especially ethambutol (EMB), has been widely reported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosyl transferase enzyme. This study aimed to detect mutations in the embB gene of Mycobacterium tuberculosis from Papua and to evaluate their impact on the effectiveness of EMB. We analyzed 20 samples of M. tuberculosis culture that had undergone whole-genome sequencing, of which 19 samples were of sufficient quality for further bioinformatics analysis. Mutation analysis was performed using TBProfiler, which identified M306L, M306V, D1024N, and E378A mutations. In sample TB035, the M306L mutation was present along with E378A. The binding affinity of EMB to arabinosyl transferase was calculated using AutoDock Vina. The molecular docking results revealed that all mutants demonstrated an increased binding affinity to EMB compared to the native protein (-0.948 kcal/mol). The presence of the M306L mutation, when coexisting with E378A, resulted in a slight increase in binding affinity compared to the M306L mutation alone. The molecular dynamics simulation results indicated that the M306L, M306L + E378A, M306V, and E378A mutants decreased protein stability. Conversely, the D1024N mutant exhibited stability comparable to the native protein. In conclusion, this study suggests that the M306L, M306L + E378A, M306V, and E378A mutations may contribute to EMB resistance, while the D1024N mutation may be consistent with continued susceptibility to EMB.

• Genomics & Informatics
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• v.5 no.3
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• pp.107-112
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• 2007

MicroRNAs (miRNAs) are known to negatively control protein-coding genes by binding to messenger RNA (mRNA) in the cytoplasm. In innate immunity, the role of miRNA gene silencing is largely unknown. In this study, we performed microarray-based experiments using lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type, MyD88 knockout (KO), TRIF KO, and MyD88/TRIF double KO mice. We employed a statistical approach to determine the importance of the commonality and specificity of miRNA binding sites among groups of temporally co-regulated genes. We demonstrate that both commonality and specificity are irrelevant to define a priori groups of co-down regulated genes. In addition, analyzing the various experimental conditions, we suggest that miRNA regulation may not only be a late-phase process (after transcription) but can also occur even early (1h) after stimulation in knockout conditions. This further indicates the existence of dynamic interactions between miRNA and signaling molecules/transcription factor regulation; this is another proof for the need of shifting from a 'hard-wired' paradigm of gene regulation to a dynamical one in which the gene co-regulation is established on a case-by-case basis.

• Genomics & Informatics
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• v.12 no.4
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• pp.268-275
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• 2014

The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.

• Journal of Animal Science and Technology
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• v.49 no.6
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• pp.719-728
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• 2007

The cysteine and glycine rich protein 3 (CSRP3), apolipoprotein B mRNA editing enzyme catalytic polypeptide‐like 2(APOBEC2) and caveolin (CAV) gene family(CAV1, CAV2, CAV3) have been reported to play important roles for carcass and meat quality traits in pig, mouse, human and cattle. As an initial step, we investigated SNPs in these 5 genes among eight different cattle breeds. Eighteen primer pairs were designed from bovine sequence data of NCBI database to amplify the partial gene fragments. Sequencing results revealed 9 SNPs in the coding regions of three caveolin genes, 1 SNP in CSRP3 and 3 SNPs in APOBEC2 gene. All the identified SNPs were confirmed by PCR-RFLP. Also, 9 more intronic SNPs were detected in these genes. However, all identified mutations in the coding region do not change amino acid sequence. Allelic distributions were significantly different for 5 SNPs in CAV2, CAV3, CSRP3 and APOBEC2 genes among the eight different breeds. These results gave some clues about the polymorphisms of these genes among the cattle breeds and will be useful for further searches for identifying association between these SNPs and meat quality traits in cattle.

• Genomics & Informatics
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• v.1 no.2
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• pp.101-107
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• 2003

Loss of heterozygosity (LOH) has been used to detect deleted regions of a specific chromosome in cancer cells. LOH on chromosome 16q has been reported to occur frequently in progressed hepatocellular carcinoma (HCC). Liver tissues from 37 Korean HCC patients were analyzed for LOH by using 25 polymorphic microsatellite markers distributed along 16q. Out of the 37 HCC patients studied, 21 patients (56.8%) showed LOH in various regions of 16q with at least one polymorphic marker. Puring the analysis of these 21 LOH cases, 6 patients showed interstitial LOHs in which the boundary of the LOH region was defined. With two rounds of LOH analysis, five commonly occurring interstitial LOH regions were identified; 16q21-22.1, 16q22.2 - 22.3, 16q22.3, 16q23.2 and 16q23.3 - 24.1. Among the five LOH regions the 16q23.3 - 24.1 region has been reported to be related with chromosome instability. A complete physical map, which covers the 3.2 Mb region of 16q23.3 - 24.1 (D16S402 and D16S486), was constructed to identify novel candidate tumor suppressor genes. We provide the minimally tiling path map consisting of 28 BAC clones. There was one gap between NT_10422.11 and NT_019609.9 of the human genome sequence contig (NCBI sequence build 33, April 29, 2003). This gap can be filled by sequencing the R-1425M20 clone which bridges these sequence contigs.

• Genomics & Informatics
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• v.14 no.3
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.208-219
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• 2001

The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

• International Journal of Industrial Entomology and Biomaterials
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• v.31 no.2
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• pp.115-126
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• 2015

The tropical climate prevailing in India adversely affects temperate bivoltine silkworm rearing and causes crop loss especially during summer. Identification of high temperature tolerant bivoltine breeds by screening for thermotolerance in the silkworm, Bombyx mori (Lepidoptera: Bombycidae) is an essential prerequisite for the development of thermotolerant bivoltine breeds / hybrids. Therefore, in this study, 20 silkworm breeds were reared at different temperatures (25 ± 1℃,32 ± 1℃, 34 ± 1℃ and 36 ± 1℃) for 6 h every day from 3^rd d of 5^th instar to till spinning. Significant differences (p < 0.01) were found among all the rearing traits over temperature. Based on pupation percentage, SK4C and BHR3 were identified as thermotolerant bivoltine breeds. Hierarchical clustering analysis based on rearing traits at tested temperatures grouped 20 silkworm breeds in four clusters which included one cluster each of susceptible and tolerant, and two clusters of moderately tolerant silkworm breeds. This suggests that clustering based on rearing data at high temperatures by using Euclidean distance can be an effective approach in classifying the silkworm breeds on their thermotolerance capacity. The identified breeds would be used for development of thermo tolerant bivoltine silkworm breeds / hybrids.