• Title/Summary/Keyword: Human genome

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A truncated form of human alpha 1-acid glycoprotein is useful as a molecular tool for insect glycobiology

  • Morokuma, Daisuke;Hino, Masato;Tsuchioka, Miho;Masuda, Akitsu;Mon, Hiroaki;Fujiyama, Kazuhito;Kajiura, Hiroyuki;Kusakabe, Takahiro;Lee, Jae Man
    • International Journal of Industrial Entomology and Biomaterials
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    • v.36 no.1
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    • pp.15-24
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    • 2018
  • N-glycosylation is an important posttranslational modification that results in a variety of biological activities, structural stability, and protein-protein interactions. There are still many mysteries in the structure and function of N-glycans, and detailed elucidation is necessary. Baculovirus expression system (BES) is widely used to produce recombinant glycoproteins, but it is not suitable for clinical use due to differences in N-glycan structure between insects and mammals. It is necessary to develop adequate model glycoproteins for analysis to efficiently alter the insect-type N-glycosylation pathway to human type. The previous research shows the recombinant alpha 1-acid glycoprotein (${\alpha}1AGP$) secreted from silkworm cultured cells or larvae is highly glycosylated and expected to be an excellent research candidate for the glycoprotein analysis expressed by BES. Therefore, we improved the ${\alpha}1AGP$ to be a better model for studying glycosylation. The modified ${\alpha}1AGP$ (${\alpha}1AGP{\Delta}$) recombinant protein was successfully expressed and purified by using BES, however, the expression level in silkworm cultured cells and larvae were lower than that of the ${\alpha}1AGP$. Subsequently, we confirmed the detailed profile of N-glycan on the ${\alpha}1AGP{\Delta}$ by LS/MS analysis the N-glycan structure at each glycosylation site. These results indicated that the recombinant ${\alpha}1AGP{\Delta}$ could be usable as a better model glycoprotein of N-glycosylation research in BES.

Phylogenetic Analysis of HERV-K LTR Family in Human Chromosome Xq26 and New World Monkeys

  • Kim, Heui-Soo;Park, Joo-Young;Lee, Won-Ho;Jang, Kyung-Lib;Park, Won-Hyuck;Moon, Doo-Ho;Osamu Takenaka;Hyun, Byung-Hwa
    • Journal of Life Science
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    • v.10 no.1
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    • pp.32-36
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    • 2000
  • Solitary long terminal repeats(LTRs) of human endogenous retrovirus K family(HERV-K) have been found to be coexpressed with sequences of closely located genes. It has been suggested that HERV-K LTR-like elements entered the primate genome approximately 33-40 million years ago. WE investigated the presence of HERV-K LTR elements in New World monkeys using PCR amplification. Six LTR elements of HERV-K family were identified from New World monkeys, represented by the squirrel and night monkeys. They showed a high degree of sequence homology(96-99%) with the human-specific HERV-K LTR elements. Phylogenetic analysis reveals that an LTR element (SM-1) from the squirrel monkey and another LTR element (NM-1) from the night monkey are very closely related to the human-specific HERV-K LTR elements with low degree of divergence. This finding suggests that some of LTR elements of HERV-K family have recently been proliferated in New World monkeys. A sequence in chromosome Xq26(AL034407) \ulcorner contains an HERV-K LTR element was shown to be present in the human genome, but is absent in the bonobo, chimpanzee, gorilla, orangutan, and gibbon. It has more than 99% homology to other human-specific HERV-K LTR elements. This sequence thus represents and isolated insertion of an evolving class of elements that may have made a particular contribution to human genomic plasticity.

African great apes (chimpanzee and gorilla) : feature, phylogeny and evolution (아프리카 대형 유인원(침팬지, 고릴라) : 특징, 계통 및 진화)

  • 홍경원;김희수
    • Journal of Life Science
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    • v.13 no.2
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    • pp.175-183
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    • 2003
  • The chimpanzee and gorilla are classified into hominidae, catarrhini, primates. These species are originated from Africa, so called African great apes. Recently, primatologists have classified that there are 2 species 5 subspecies of the chimpanzee and gorilla, respectively. Since the human genome project has been finished, the chimpanzee genome project has been launched to understand human evolution and genetic diseases. The sequences of chimpanzee chromosome 22 homologous to human chromosome 21 were completed, and then the Y chromosome of chimpanzee is being analyzed. Comparative analysis of human, chimpanzee and gorilla could provide the key for understanding of various human diseases and human origin. By detecting human specific-functional genes or mobile genetic elements (HERV, LINE, SINE) through primate research, we could understand what is human being\ulcorner gradually, For these comparative researches, we summarized fundamental knowledge of the feature, phylogeny and evolution of African great apes including humans.

Analysis of unmapped regions associated with long deletions in Korean whole genome sequences based on short read data

  • Lee, Yuna;Park, Kiejung;Koh, Insong
    • Genomics & Informatics
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    • v.17 no.4
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    • pp.40.1-40.9
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    • 2019
  • While studies aimed at detecting and analyzing indels or single nucleotide polymorphisms within human genomic sequences have been actively conducted, studies on detecting long insertions/deletions are not easy to orchestrate. For the last 10 years, the availability of long read data of human genomes from PacBio or Nanopore platforms has increased, which makes it easier to detect long insertions/deletions. However, because long read data have a critical disadvantage due to their relatively high cost, many next generation sequencing data are produced mainly by short read sequencing machines. Here, we constructed programs to detect so-called unmapped regions (UMRs, where no reads are mapped on the reference genome), scanned 40 Korean genomes to select UMR long deletion candidates, and compared the candidates with the long deletion break points within the genomes available from the 1000 Genomes Project (1KGP). An average of about 36,000 UMRs were found in the 40 Korean genomes tested, 284 UMRs were common across the 40 genomes, and a total of 37,943 UMRs were found. Compared with the 74,045 break points provided by the 1KGP, 30,698 UMRs overlapped. As the number of compared samples increased from 1 to 40, the number of UMRs that overlapped with the break points also increased. This eventually reached a peak of 80.9% of the total UMRs found in this study. As the total number of overlapped UMRs could probably grow to encompass 74,045 break points with the inclusion of more Korean genomes, this approach could be practically useful for studies on long deletions utilizing short read data.

Identifying Copy Number Variants under Selection in Geographically Structured Populations Based on F-statistics

  • Song, Hae-Hiang;Hu, Hae-Jin;Seok, In-Hae;Chung, Yeun-Jun
    • Genomics & Informatics
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    • v.10 no.2
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    • pp.81-87
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    • 2012
  • Large-scale copy number variants (CNVs) in the human provide the raw material for delineating population differences, as natural selection may have affected at least some of the CNVs thus far discovered. Although the examination of relatively large numbers of specific ethnic groups has recently started in regard to inter-ethnic group differences in CNVs, identifying and understanding particular instances of natural selection have not been performed. The traditional $F_{ST}$ measure, obtained from differences in allele frequencies between populations, has been used to identify CNVs loci subject to geographically varying selection. Here, we review advances and the application of multinomial-Dirichlet likelihood methods of inference for identifying genome regions that have been subject to natural selection with the $F_{ST}$ estimates. The contents of presentation are not new; however, this review clarifies how the application of the methods to CNV data, which remains largely unexplored, is possible. A hierarchical Bayesian method, which is implemented via Markov Chain Monte Carlo, estimates locus-specific $F_{ST}$ and can identify outlying CNVs loci with large values of FST. By applying this Bayesian method to the publicly available CNV data, we identified the CNV loci that show signals of natural selection, which may elucidate the genetic basis of human disease and diversity.

Mining the Proteome of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 for Potential Therapeutics Discovery: An In Silico Approach

  • Habib, Abdul Musaweer;Islam, Md. Saiful;Sohel, Md.;Mazumder, Md. Habibul Hasan;Sikder, Mohd. Omar Faruk;Shahik, Shah Md.
    • Genomics & Informatics
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    • v.14 no.4
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    • pp.255-264
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    • 2016
  • The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

Genome-Wide Association Study between Copy Number Variation and Trans-Gene Expression by Protein-Protein Interaction-Network (단백질 상호작용 네트워크를 통한 유전체 단위반복변이와 트랜스유전자 발현과의 연관성 분석)

  • Park, Chi-Hyun;Ahn, Jae-Gyoon;Yoon, Young-Mi;Park, Sang-Hyun
    • The KIPS Transactions:PartD
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    • v.18D no.2
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    • pp.89-100
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    • 2011
  • The CNV (Copy Number Variation) which is one of the genetic structural variations in human genome is closely related with the function of gene. In particular, the genome-wide association studies for genetic diseased persons have been researched. However, there have been few studies which infer the genetic function of CNV with normal human. In this paper, we propose the analysis method to reveal the functional relationship between common CNV and genes without considering their genomic loci. To achieve that, we propose the data integration method for heterogeneity biological data and novel measurement which can calculate the correlation between common CNV and genes. To verify the significance of proposed method, we has experimented several verification tests with GO database. The result showed that the novel measurement had enough significance compared with random test and the proposed method could systematically produce the candidates of genetic function which have strong correlation with common CNV.

Can herbal drug(s) meet the challenges of genomewide screen results on rheumatoid arthritis

  • Paul, Bholanath
    • Advances in Traditional Medicine
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    • v.5 no.4
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    • pp.251-261
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    • 2005
  • Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. RA is characterized by chronic inflammation of the synovial membrane in the joint, which leads to the progressive destruction of articular cartilage, ligament and bone. Several cytokines such as tumor necrosis $factor-{\alpha}\;TNF-{\alpha}\;and\;interleukin-1{\beta}\;(IL-1{\beta})$ and interleukin-6 (IL-6) have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. Genome wide screening of subjects suffering from autoimmune diseases especially arthritis revealed linkage to inflammatory molecules like $TNF-{\alpha},\;IL-1{\beta}$ and IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB $(NF-{\kappa}B)$ and human leucocyte antigen/major histocompatibility complex (HLA/MHC) locus. The status of the pharmacological mechanism of herbal drugs in the light of genome wide screening results has been discussed to reinforce the therapeutic potential and the pharmacological basis of the herbal drugs.