• Title/Summary/Keyword: 3D genomics

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Therapeutic Strategy for the Prevention of Pseudorabies Virus Infection in C57BL/6 Mice by 3D8 scFv with Intrinsic Nuclease Activity

  • Lee, Gunsup;Cho, SeungChan;Hoang, Phuong Mai;Kim, Dongjun;Lee, Yongjun;Kil, Eui-Joon;Byun, Sung-June;Lee, Taek-Kyun;Kim, Dae-Hyun;Kim, Sunghan;Lee, Sukchan
    • Molecules and Cells
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    • v.38 no.9
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    • pp.773-780
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    • 2015
  • 3D8 single chain variable fragment (scFv) is a recombinant monoclonal antibody with nuclease activity that was originally isolated from autoimmune-prone MRL mice. In a previous study, we analyzed the nuclease activity of 3D8 scFv and determined that a HeLa cell line expressing 3D8 scFv conferred resistance to herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV). In this study, we demonstrate that 3D8 scFv could be delivered to target tissues and cells where it exerted a therapeutic effect against PRV. PRV was inoculated via intramuscular injection, and 3D8 scFv was injected intraperitoneally. The observed therapeutic effect of 3D8 scFv against PRV was also supported by results from quantitative reverse transcription polymerase chain reaction, southern hybridization, and immunohistochemical assays. Intraperitoneal injection of 5 and $10{\mu}g$ 3D8 scFv resulted in no detectable toxicity. The survival rate in C57BL/6 mice was 9% after intramuscular injection of 10 $LD_{50}$ PRV. In contrast, the 3D8 scFv-injected C57BL/6 mice showed survival rates of 57% ($5{\mu}g$) and 47% ($10{\mu}g$). The results indicate that 3D8 scFv could be utilized as an effective antiviral agent in several animal models.

Recent Trend of Research Activity on Marine Biotechnology in China (중국의 해양생명공학 연구개발 최근 동향)

  • Kim, Sang-Jin;Jianhai, Xiang
    • Ocean and Polar Research
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    • v.26 no.2
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    • pp.165-172
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    • 2004
  • Research activities on the fields of marine biotechnology becomes active not only in developing countries but also in Asian countries. Among those countries China recently initiate the national marine biotechnology R&D program. Since 1996, marine biotechnology has been approved to be a subject of the National High Technology Research and Development Program of China as 863 program. In the first five years from 1996 to 2000 and successively in the second five years from 2001 to 2005, Marine Biotechnology R&D 863 program has been funded by Chinese government with 97.5 million RMB and then more than 200 million RMB, respectively. Under this program there are mainly six R&D subjects of marine biotechnology; 1. Breeding engineering, 2. Control of the disease, 3. Production system and culture facilities, 4. Marine drug and bioproducts, 5. Functional genes and genomics, 6. Breeding of the saltresistant plants. In this paper the research activities and results of 863 program were introduced, and from chinese cases we could leam how we plan and perform the marine biotechnology program of Korea in future.

Frequency of the Angiotensin - Converting Enzyme (ACE) Gene Polymorphism in the General Population and the Elite Endurance Students in Korea

  • Choung, Ho-Jin;Yoon, Song-Ro;Choi, Soo-Kyung
    • Journal of Genetic Medicine
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    • v.3 no.1
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    • pp.11-13
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    • 1999
  • Recently it was reported that Insertion/Deletion polymorphism in the gene coding for Angiotensin-Converting Enzyme (ACE) is associated with human capacity for physical performance. This study was performed to genotyping of the ACE gene to determine the correlation between elite endurance performance and ACE I/D gene polymorphism. DNA sample was obtained from peripheral blood, hair roots and mouth epithelial cell in 739 general population and 200 elite athletic performance students. The ACE gene was amplified by polymerase chain reaction (PCR) using allele specific oligonucleotide primers. 155, 525 bp and 237 bp PCR products indicating the presence of insertion(I) and deletion(D) alleles, respectively, were clearly resolved after electrophoresis on a 2% agarose gel with ethidium bromide. Of the 200 elite athletic performance population subjects, 68(34%) showed ACE genotype 11,100(50%) genotype ID and 32(16%) genotype DD. Of the 739 general population subjects, 259(35.1%) showed ACE genotype 11,363(49.1%) genotype ID and 117(15.8%) genotype DD. Therefore ACE I/D gene polymorphism was not associated with human capacity for physical performance.(p>0.05)

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Molecular insights into the role of genetic determinants of congenital hypothyroidism

  • Kollati, Yedukondalu;Akella, Radha Rama Devi;Naushad, Shaik Mohammad;Patel, Rajesh K.;Reddy, G. Bhanuprakash;Dirisala, Vijaya R.
    • Genomics & Informatics
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    • v.19 no.3
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    • pp.29.1-29.10
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    • 2021
  • In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level. In TSHR variants (rs2268477, rs7144481, and rs17630128), the binding affinity of microRNAs (miRs) (hsa-miR-154-5p, hsa-miR-376a-2-5p, hsa-miR-3935, hsa-miR-4280, and hsa-miR-6858-3p) to the 3'-UTR is disrupted, affecting post-transcriptional gene regulation. TPO and TG are the two key proteins necessary for the biosynthesis of thyroid hormones in the presence of iodide and H2O2. Reduced stability of these proteins leads to aberrant biosynthesis of thyroid hormones. Compared to the wild-type TPO protein, the p.S398T variant was found to exhibit less stability and significant rearrangements of intra-atomic bonds affecting the stoichiometry and substrate binding (binding energies, ΔG of wild-type vs. mutant: -15 vs. -13.8 kcal/mol; and dissociation constant, Kd of wild-type vs. mutant: 7.2E-12 vs. 7.0E-11 M). The missense mutations p.G653D and p.R1999W on the TG protein showed altered ΔG(0.24 kcal/mol and 0.79 kcal/mol, respectively). In conclusion, an in silico analysis of TSHR genetic variants in the 3'-UTR showed that they alter the binding affinities of different miRs. The TPO protein structure and mutant protein complex (p.S398T) are less stable, with potentially deleterious effects. A structural and energy analysis showed that TG mutations (p.G653D and p.R1999W) reduce the stability of the TG protein and affect its structure-functional relationship.

Molecular Cloning of cDNA Encoding a Putative Eugenol Synthase in Tomato (Solanum lycopersicum 'Micro-Tom') and Prediction of 3D Structure and Physiochemical Properties (토마토 'Micro-Tom' 과실의 eugenol synthase 유전자 클로닝, 단백질의 3차 구조 및 생리화학적 특성 예측)

  • Kang, Seung-Won;Seo, Sang-Gyu;Lee, Tai-Ho;Lee, Gung-Pyo
    • Journal of agriculture & life science
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    • v.46 no.4
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    • pp.9-20
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    • 2012
  • Eugenol is a volatile compound synthesized by eugenol synthase in various plants and belongs to phenylpropene compounds. However, characteristics of eugenol synthase in tomato has not been known. Therefore, we cloned a full length cDNA of a putative eugenol synthase from tomato 'Micro-Tom' using rapid amplification of cDNA ends (RACE) technique and named a clone SlEGS. Open reading frame of SlEGS was 921bp long and its deduced amino acid sequence was 307bp. The BLAST analysis indicated that SlEGS shared high similarity with PhEGS1 (67.1%) and CbEGS2 (69.4%). Amino acid composition of SlEGS was determined by CLC genomics workbench tool and 3D structure of SlEGS was constructed by homology modeling using Swiss-PDB viewer and validated using PROCHECK and ProSA-web tool. In addition, the physiochemical properties of SlEGS was evaluated using ExPASy's ProtParam tool. Molecular weight was 33.93kDa and isoelectric point was 5.85 showing acidic nature. Other properties such as extinction coefficient, instability index, aliphatic index, and grand average hydropathy was also analyzed.

Localization of Quantitative Trait Loci for Bone Mineral Density on Chromosome 13 in the Mongolian Population

  • Seo, Soo-Hyun;Lim, Hae-Jeng;Ahn, Se-Jin;Lee, Joseph;Kim, Jong-Il
    • Genomics & Informatics
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    • v.7 no.3
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    • pp.152-158
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    • 2009
  • Although the genetic basis for bone mineral density (BMD) has been studied by many groups so far, genes responsible for this complex trait has not been completely revealed. In order to localize quantitative trait loci (QTLs) for BMD variation in Asian population, the study was designed using a group of Mongolian population, a genetically closed population with a homogeneous lifestyle. BMD was measured at the left and right wrists and ankles using DEXA in 1,082 participants from 142 families. Genotyping of 13 polymorphic microsatellite markers on chromosome 13 (average spacing 8-9 cM) and two-point and multipoint linkage analysis were performed. In two-point linkage analysis, we identified two markers, D13S175 (6.03 cM) and D13S265 (68.73 cM) that had LOD scores greater than 1 for left ankle (LOD=2.09, LOD=1.49, respectively). We also found a marker D13S175 (6.03 cM) with a high LOD for left wrist (LOD=1.49) and the markers D13S265 (68.73 cM) and D13S217 (17.21 cM) for the right wrist (LOD= 1.82, LOD= 1.62, respectively). Among these significant marker regions, only two regions at 17 cM (13p11) and 65 cM (13q21) for the right wrist overlapped with major QTLs reported in following multipoint linkage analysis (LOD= 1.7549, LOD=1.4462, respectively). This study provides the possible evidence of the presence of QTLs affecting right wrist BMD in Mongolian populations on 13p11 and 13q21. Modest evidence was also found for genes affecting left ankle and left wrist BMD on 13p13.

DNA Polymorphisms in SREBF1 and FASN Genes Affect Fatty Acid Composition in Korean Cattle (Hanwoo)

  • Bhuiyan, M.S.A.;Yu, S.L.;Jeon, J.T.;Yoon, D.;Cho, Y.M.;Park, E.W.;Kim, N.K.;Kim, K.S.;Lee, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.6
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    • pp.765-773
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    • 2009
  • Sterol regulatory element binding factor 1 (SREBF1) and fatty acid synthase (FASN) genes play an important role in the biosynthesis of fatty acids and cholesterol, and in lipid metabolism. This study used polymorphisms in the intron 5 of bovine SREBF1 and in the thioesterase (TE) domain of FASN genes to evaluate their associations with beef fatty acid composition. A previously identified 84-bp indel (L: insertion/long type and S: deletion/short type) of the SREBF1 gene in Korean cattle had significant associations with the concentration of stearic (C18:0), linoleic (C18:2) and polyunsaturated fatty acids (PUFA). The stearic acid concentration was 6.30% lower in the SS than the LL genotype (p<0.05), but the linoleic and PUFA contents were 11.06% and 12.20% higher in SS compared to LL (p<0.05). Based on the sequence analysis, five single nucleotide polymorphisms (SNPs) g.17924G>A, g.18043C>T, g.18440G>A, g.18529G>A and g.18663C>T in the TE domain of the FASN gene were identified among the different cattle breeds studied. Among these, only g.17924 G>A and g.18663C>T SNPs were segregating in the Hanwoo population. The g.17924G>A SNP is a non-synonymous mutation (thr2264ala) and was significantly associated with the contents of palmitic (C16:0) and oleic acid (C18:1). The oleic acid concentration was 3.18% and 2.79% higher in Hanwoo with the GG genotype than the AA and AG genotypes, respectively (p<0.05), whereas the GG genotype had 3.8% and 4.01% lower palmitic acid than in those cattle with genotype AA and AG, respectively (p<0.05). Tissue expression data showed that SREBFI and FASN genes were expressed in a variety of tissues though they were expressed preferentially in different muscle tissues. In conclusion, the 84-bp indel of SREBF1 and g.17924G>A SNP of the FASN gene can be used as DNA markers to select Hanwoo breeding stock for fatty acid composition.

A Novel Insertion in Exon 23 of the TCOF1 Gene in a Newborn Infant with Treacher Collins Syndrome

  • Yang, Ji Hyeon;Cha, Hyo Hyun;Yoon, Hye Sun
    • Journal of Genetic Medicine
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    • v.10 no.2
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    • pp.109-112
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    • 2013
  • Treacher Collins syndrome (TCS) is the most common and well known mandibulofacial dysostosis with characteristic clinical features including downward slanting of palpebral fissures, coloboma of the lower eyelid, hypoplastic zygomatic arches, micrognathia, macrostomia, microtia, and other deformities of the ears. TCS is caused by mutations in at least 3 genes involved in pre-rRNA transcription: TCOF1, POLR1D and POLR1C. We experienced a 1-day-old female infant with characteristic clinical features of TCS. A novel, heterozygotic mutation within the TCOF1 gene (c.3874_3875insG, p.Ala1292Glyfs*30) was identified to cause a premature stop codon.

The Atom of Evolution

  • Bhak, Jonghwa;Bolser, Dan;Park, Daeui;Cho, Yoobok;Yoo, Kiesuk;Lee, Semin;Gong, SungSam;Jang, Insoo;Park, Changbum;Huston, Maryana;Choi, Hwanho
    • Genomics & Informatics
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    • v.2 no.4
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    • pp.167-173
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    • 2004
  • The main mechanism of evolution is that biological entities change, are selected, and reproduce. We propose a different concept in terms of the main agent or atom of evolution: in the biological world, not an individual object, but its interactive network is the fundamental unit of evolution. The interaction network is composed of interaction pairs of information objects that have order information. This indicates a paradigm shift from 3D biological objects to an abstract network of information entities as the primary agent of evolution. It forces us to change our views about how organisms evolve and therefore the methods we use to analyze evolution.

Topological implications of DNA tumor viral episomes

  • Eui Tae, Kim;Kyoung-Dong, Kim
    • BMB Reports
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    • v.55 no.12
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    • pp.587-594
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    • 2022
  • A persistent DNA tumor virus infection transforms normal cells into cancer cells by either integrating its genome into host chromosomes or retaining it as an extrachromosomal entity called episome. Viruses have evolved mechanisms for attaching episomes to infected host cell chromatin to efficiently segregate the viral genome during mitosis. It has been reported that viral episome can affect the gene expression of the host chromosomes through interactions between viral episomes and epigenetic regulatory host factors. This mini review summarizes our current knowledge of the tethering sites of viral episomes, such as EBV, KSHV, and HBV, on host chromosomes analyzed by three-dimensional genomic tools.