• Genomics & Informatics
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• v.12 no.4
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• pp.225-230
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• 2014

Platelets are derived from the fragments that are formed from the cytoplasm of bone marrow megakaryocytes-small irregularly shaped anuclear cells. Platelets respond to vascular damage, contracts blood vessels, and attaches to the damaged region, thereby stopping bleeding, together with the action of blood coagulation factors. Platelet activation is known to affect genes associated with vascular risk factors, as well as with arteriosclerosis and myocardial infarction. Here, we performed a genome-wide association study with 352,228 single-nucleotide polymorphisms typed in 8,842 subjects of the Korea Association Resource (KARE) project and replicated the results in 7,861 subjects from an independent population. We identified genetic associations between platelet count and common variants nearby chromosome 4p16.1 ($p=1.46{\times}10^{10}$, in the KIAA0232 gene), 6p21 ($p=1.36{\times}10^{-7}$, in the BAK1 gene), and 12q24.12 ($p=1.11{\times}10^{-15}$, in the SH2B3 gene). Our results illustrate the value of large-scale discovery and a focus for several novel research avenues.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04b
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• pp.19-25
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• 2002

Biotechnology in the 21st century will be driven by three emerging technologies: genomics, high-throughput biology, and bioinformatics. These technologies are complementary to one another. A large number of economically important crops are currently subjected to whole genome sequencing. Functional genomics for determining the functions of the genes comprising the given plant genome is under progress by using various means including phenotyping data from transgenic mutants, gene expression profiling data from DNA microarrays, and metabolic profiling data from LC/mass analysis. The aim of plant molecular breeding is shifting from introducing agronomic traits such as herbicide and insect resistance to introducing quality traits such as healthful oils and proteins, which will lead to improved and nutritional food and feed products. Plant molecular breeding is also expected to aim to develop crops for producing human therapeutic and industrial proteins.

• Genomics & Informatics
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• v.9 no.4
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• pp.152-160
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• 2011

Hypertension is the major factor of most death and high blood pressure (BP) can lead to stroke, myocardial infarction and cardiac failure. Moreover, hypertension is strongly correlated with body mass index (BMI). Although the exact causes of hypertension are still unclear, some of genetic loci were discovered from genome-wide association study (GWAS). Therefore, it is essential to study genetic variation for finding more genetic factor affecting hypertension. The purpose of our study is to conduct a CNV association study for hypertension-related traits, BP and BMI, in Korean individuals. We identified 2,206 CNV regions from 3,274 community-based Korean participants using the Affymetrix Genome-Wide Human SNP Array 6.0 platform and performed a logistic regression analysis of CNVs with two hypertension-related traits, BP and BMI. Moreover, the 4,692 participants in an independent cohort were selected for respective replication analyses. GWAS of CNV identified two loci encompassing previously known hypertension-related genes: LPA (lipoprotein) on 6q26, and JAK2 (Janus kinase 2) on 9p24, with suggestive p-values (0.0334 for LPA and 0.0305 for JAK2 ). These two positive findings, however, were not evaluated in the replication stage. Our result confirmed the conclusion of CNV study from the WTCCC suggesting weak association with common diseases. This is the first study of CNV association study with BP and BMI in Korean population and it provides a state of CNV association study with common human diseases using SNP array.

• BMB Reports
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• v.45 no.6
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• pp.365-370
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• 2012

Hepatitis B virus (HBV) DNA is often integrated into hepatocellular carcinoma (HCC). Although the relationship between HBV integration and HCC development has been widely studied, the role of HBV integration in HCC development is still not completely understood. In the present study, we constructed a pooled BAC library of 9 established cell lines derived from HCC patients with HBV infections. By amplifying viral genes and superpooling of BAC clones, we identified 2 clones harboring integrated HBV DNA. Screening of host-virus junctions by repeated sequencing revealed an HBV DNA integration site on chromosome 11q13 in the SNU-886 cell line. The structure and rearrangement of integrated HBV DNA were extensively analyzed. An inverted duplicated structure, with fusion of at least 2 HBV DNA molecules in opposite orientations, was identified in the region. The gene expression of cancer-related genes increased near the viral integration site in HCC cell line SNU-886.

• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1059-1063
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• 2008

Abnormal phenotypes resulting from haploinsufficiency (HI) are due to the loss of one allele. Recent studies in budding yeast have shown that HI originates from insufficient protein levels or from a stoichiometric imbalance between subunits of protein complexes. In humans, however, HI often involves transcription factors. Therefore, the species differences in HI and the molecular mechanisms of species-specific HI remain under investigation. In this study, HI in fission yeast was systematically surveyed. HI in fission yeast affected genes related to signaling and to basic cellular processes, as observed in budding yeast. These results suggest that there are species differences in HI and that the HI that occurs in fission yeast is intermediate to HI in budding yeast and humans.

• Molecules and Cells
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• v.45 no.8
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• pp.550-563
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• 2022

Hepatocellular carcinoma (HCC) is an aggressive and incurable cancer. Although understanding of the molecular pathogenesis of HCC has greatly advanced, therapeutic options for the disease remain limited. In this study, we demonstrated that SETD5 expression is positively associated with poor prognosis of HCC and that SETD5 depletion decreased HCC cell proliferation and invasion while inducing cell death. Transcriptome analysis revealed that SETD5 loss downregulated the interferon-mediated inflammatory response in HCC cells. In addition, SETD5 depletion downregulated the expression of a critical glycolysis gene, PKM (pyruvate kinase M1/2), and decreased glycolysis activity in HCC cells. Finally, SETD5 knockdown inhibited tumor growth in xenograft mouse models. These results collectively suggest that SETD5 is involved in the tumorigenic features of HCC cells and that targeting SETD5 may suppress HCC progression.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2005.04a
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• pp.12-14
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• 2005

• BMB Reports
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• v.48 no.2
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• pp.81-90
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• 2015

p73 is a structural and functional homologue of the p53 tumor suppressor protein. Like p53, p73 induces apoptosis and cell cycle arrest and transactivates p53-responsive genes, conferring its tumor suppressive activity. In addition, p73 has unique roles in neuronal development and differentiation. The importance of p73-induced apoptosis lies in its capability to substitute the pro-apoptotic activity of p53 in various human cancer cells in which p53 is mutated or inactive. Despite the great importance of p73-induced apoptosis in cancer therapy, little is known about the molecular basis of p73-induced apoptosis. In this review, we discuss the p73 structures reported to date, detailed structural comparisons between p73 and p53, and current understanding of the transcription-dependent and -independent mechanisms of p73-induced apoptosis.

• Proceedings of the Microbiological Society of Korea Conference
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• 2002.10a
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• pp.3-14
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• 2002

Functional genomics aims at uncovering useful information carried on genome sequences and at using it to understand the mechanisms of biological function. Elucidating the unknown biological functions of new genes based upon the genomics rationales will greatly speed up the extensive understanding of biocatalysis and biodegradation in biological world including microorganisms. DNA microarrays generate a system for the simultaneous measurement of the expression level of thousands of genes in a single hybridization assay. Their data mining (transcriptome) strategy has two categories: differential gene expression and coordinated gene expression. Furthermore, measurement of proteins (proteome) generates information on how the transcribed sequences end up as functional characteristics within the cell, and quantitation of metabolites yields information on how the functional proteins act to produce energy and process substrates (metabolome). Various composite functional genomics databases containing genetic, enzymatic and metabolic information have been developed and will contribute to the understanding of the life blue print and the new discoveries and practices in biocatalysis and biodegradation that could enrich their industrial and environmental applications.

• Molecules and Cells
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• v.26 no.5
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• pp.468-473
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• 2008

Low-density lipoprotein (LDL) induces cell proliferation in human aortic smooth muscle cells (hAoSMCs), which may be involved in atherogenesis and intimal hyperplasia. Recent studies have demonstrated that $Cl^-$ channels are related to vessel cell proliferation induced by a variety of stimuli. In this study, we investigated a potential role of $Cl^-$ channels in the signaling pathway of LDL effects on hAoSMC proliferation with a focus on the activation of Erk1/2-PI3K/Akt and the subsequent upregulation of Egr-1. $Cl^-$ channel blockers, DIDS, but neither NPPB nor Furosemide, completely abolished the LDL-induced DNA synthesis and cell proliferation. Moreover, DIDS, but not NPPB, significantly decreased LDL-stimulated $Cl^-$ concentration, as judged by flow cytometry analysis using MQAE as a $Cl^-$-detection dye. DIDS pretreatment completely abolished the activation of Erk1/2 and PI3K/Akt in a dose-dependent manner that is the hallmark of LDL activation, as judged by Western blot and proliferation assays. Moreover, pretreatment with DIDS ($Cl^-$ channel blockers) but not LY294002 (PI3K inhibitors) completely abolished the LDL-induced upregulation of Egr-1 to the same extent as PD98059 (MEK inhibitors to inhibit Erk), as judged by Western blot and luciferase reporter assays. This is the first report, to our knowledge, that DIDS-sensitive $Cl^-$-channels play a key role in the LDL-induced cell proliferation of hAoSMCs via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1.