請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84483完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 顏伯勳(Bo-Shiun Yan) | |
| dc.contributor.author | Tzu-Yin Chen | en |
| dc.contributor.author | 陳姿吟 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:13:02Z | - |
| dc.date.copyright | 2022-10-13 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-23 | |
| dc.identifier.citation | 1 Runyon, E. H. Anonymous mycobacteria in pulmonary disease. Med Clin North Am 43, 273-290, doi:10.1016/s0025-7125(16)34193-1 (1959). 2 Ding, L. W., Lai, C. C., Lee, L. N. et al. Disease caused by non-tuberculous mycobacteria in a university hospital in Taiwan, 1997-2003. Epidemiol Infect 134, 1060-1067, doi:10.1017/s0950268805005698 (2006). 3 Griffith, D. E., Aksamit, T., Brown-Elliott, B. A. et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 175, 367-416, doi:10.1164/rccm.200604-571ST (2007). 4 Falkinham, J. O., 3rd. Nontuberculous mycobacteria from household plumbing of patients with nontuberculous mycobacteria disease. Emerg Infect Dis 17, 419-424, doi:10.3201/eid1703.101510 (2011). 5 Honda, J. R., Virdi, R. & Chan, E. D. Global Environmental Nontuberculous Mycobacteria and Their Contemporaneous Man-Made and Natural Niches. Front Microbiol 9, 2029, doi:10.3389/fmicb.2018.02029 (2018). 6 To, K., Cao, R., Yegiazaryan, A. et al. General Overview of Nontuberculous Mycobacteria Opportunistic Pathogens: Mycobacterium avium and Mycobacterium abscessus. J Clin Med 9, doi:10.3390/jcm9082541 (2020). 7 van Ingen, J., Egelund, E. F., Levin, A. et al. The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment. Am J Respir Crit Care Med 186, 559-565, doi:10.1164/rccm.201204-0682OC (2012). 8 Gupta, N., Mittal, A., Niyas, V. K. M. et al. Nontuberculous mycobacteria: A report of eighteen cases from a tertiary care center in India. Lung India 37, 495-500, doi:10.4103/lungindia.lungindia_365_19 (2020). 9 Shahraki, A. H., Heidarieh, P., Bostanabad, S. Z. et al. 'Multidrug-resistant tuberculosis' may be nontuberculous mycobacteria. Eur J Intern Med 26, 279-284, doi:10.1016/j.ejim.2015.03.001 (2015). 10 Byrd, T. F. & Lyons, C. R. Preliminary characterization of a Mycobacterium abscessus mutant in human and murine models of infection. Infect Immun 67, 4700-4707, doi:10.1128/iai.67.9.4700-4707.1999 (1999). 11 Bernut, A., Nguyen-Chi, M., Halloum, I. et al. Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking. PLoS Pathog 12, e1005986, doi:10.1371/journal.ppat.1005986 (2016). 12 Thornton, C. S., Mellett, M., Jarand, J. et al. The respiratory microbiome and nontuberculous mycobacteria: an emerging concern in human health. Eur Respir Rev 30, doi:10.1183/16000617.0299-2020 (2021). 13 Roux, A. L., Viljoen, A., Bah, A. et al. The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages. Open Biol 6, doi:10.1098/rsob.160185 (2016). 14 Bernut, A., Herrmann, J. L., Kissa, K. et al. Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation. Proc Natl Acad Sci U S A 111, E943-952, doi:10.1073/pnas.1321390111 (2014). 15 Johansen, M. D., Herrmann, J. L. & Kremer, L. Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus. Nat Rev Microbiol 18, 392-407, doi:10.1038/s41579-020-0331-1 (2020). 16 Early, J., Fischer, K. & Bermudez, L. E. Mycobacterium avium uses apoptotic macrophages as tools for spreading. Microb Pathog 50, 132-139, doi:10.1016/j.micpath.2010.12.004 (2011). 17 Koh, W. J., Kwon, O. J., Jeon, K. et al. Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea. Chest 129, 341-348, doi:10.1378/chest.129.2.341 (2006). 18 van Ingen, J., Bendien, S. A., de Lange, W. C. et al. Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, The Netherlands. Thorax 64, 502-506, doi:10.1136/thx.2008.110957 (2009). 19 Shu, C. C., Wu, M. F., Pan, S. W. et al. Host immune response against environmental nontuberculous mycobacteria and the risk populations of nontuberculous mycobacterial lung disease. J Formos Med Assoc 119 Suppl 1, S13-s22, doi:10.1016/j.jfma.2020.05.001 (2020). 20 Honda, J. R., Knight, V. & Chan, E. D. Pathogenesis and risk factors for nontuberculous mycobacterial lung disease. Clin Chest Med 36, 1-11, doi:10.1016/j.ccm.2014.10.001 (2015). 21 Andréjak, C., Nielsen, R., Thomsen, V. et al. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax 68, 256-262, doi:10.1136/thoraxjnl-2012-201772 (2013). 22 Iseman, M. D., Buschman, D. L. & Ackerson, L. M. Pectus excavatum and scoliosis. Thoracic anomalies associated with pulmonary disease caused by Mycobacterium avium complex. Am Rev Respir Dis 144, 914-916, doi:10.1164/ajrccm/144.4.914 (1991). 23 Iseman, M. D. & Marras, T. K. The importance of nontuberculous mycobacterial lung disease. Am J Respir Crit Care Med 178, 999-1000, doi:10.1164/rccm.200808-1258ED (2008). 24 Lai, C. C., Tan, C. K., Chou, C. H. et al. Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000-2008. Emerg Infect Dis 16, 294-296, doi:10.3201/eid1602.090675 (2010). 25 Bush, W. S. & Moore, J. H. Chapter 11: Genome-wide association studies. PLoS Comput Biol 8, e1002822, doi:10.1371/journal.pcbi.1002822 (2012). 26 Deng, N., Zhou, H., Fan, H. et al. Single nucleotide polymorphisms and cancer susceptibility. Oncotarget 8, 110635-110649, doi:10.18632/oncotarget.22372 (2017). 27 Heap, G. A., Trynka, G., Jansen, R. C. et al. Complex nature of SNP genotype effects on gene expression in primary human leucocytes. BMC Med Genomics 2, 1, doi:10.1186/1755-8794-2-1 (2009). 28 Zaphiropoulos, P. G. Genetic variations and alternative splicing: the Glioma associated oncogene 1, GLI1. Front Genet 3, 119, doi:10.3389/fgene.2012.00119 (2012). 29 Huang, Y., Rall, S. C., Jr. & Mahley, R. W. Genetic factors precipitating type III hyperlipoproteinemia in hypolipidemic transgenic mice expressing human apolipoprotein E2. Arterioscler Thromb Vasc Biol 17, 2817-2824, doi:10.1161/01.atv.17.11.2817 (1997). 30 Liu, C. C., Liu, C. C., Kanekiyo, T. et al. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 9, 106-118, doi:10.1038/nrneurol.2012.263 (2013). 31 Uffelmann, E., Huang, Q. Q., Munung, N. S. et al. Genome-wide association studies. Nature Reviews Methods Primers 1, 1-21 (2021). 32 Herbert, A., Gerry, N. P., McQueen, M. B. et al. A common genetic variant is associated with adult and childhood obesity. Science 312, 279-283, doi:10.1126/science.1124779 (2006). 33 Samani, N. J., Erdmann, J., Hall, A. S. et al. Genomewide association analysis of coronary artery disease. N Engl J Med 357, 443-453, doi:10.1056/NEJMoa072366 (2007). 34 Saxena, R., Voight, B. F., Lyssenko, V. et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331-1336, doi:10.1126/science.1142358 (2007). 35 Wu, M. F., Shu, C. C., Wang, J. Y. et al. NLRP3 inflammasome is attenuated in patients with Mycobacterium avium complex lung disease and correlated with decreased interleukin-1β response and host susceptibility. Sci Rep 9, 12534, doi:10.1038/s41598-019-47609-3 (2019). 36 Halstrom, S., Thomson, R., Goullee, H. et al. Susceptibility to non-tuberculous mycobacterial disease is influenced by rs1518111 in IL10. Hum Immunol 78, 391-393, doi:10.1016/j.humimm.2017.02.001 (2017). 37 Cho, J., Park, K., Choi, S. M. et al. Genome-wide association study of non-tuberculous mycobacterial pulmonary disease. Thorax 76, 169-177, doi:10.1136/thoraxjnl-2019-214430 (2021). 38 Namkoong, H., Omae, Y., Asakura, T. et al. Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease. Eur Respir J 58, doi:10.1183/13993003.02269-2019 (2021). 39 Nomura, N., Miyajima, N., Sazuka, T. et al. Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1. DNA Res 1, 27-35, doi:10.1093/dnares/1.1.27 (1994). 40 Nagase, T., Koga, H. & Ohara, O. Kazusa mammalian cDNA resources: towards functional characterization of KIAA gene products. Brief Funct Genomic Proteomic 5, 4-7, doi:10.1093/bfgp/ell005 (2006). 41 Kikuno, R., Nagase, T., Nakayama, M. et al. HUGE: a database for human KIAA proteins, a 2004 update integrating HUGEppi and ROUGE. Nucleic Acids Res 32, D502-504, doi:10.1093/nar/gkh035 (2004). 42 Nagase, T., Kikuno, R. & Ohara, O. The Kazusa cDNA project for identification of unknown human transcripts. C R Biol 326, 959-966, doi:10.1016/j.crvi.2003.09.020 (2003). 43 Ullah, I., Kakar, N., Schrauwen, I. et al. Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly. Hum Genet 138, 593-600, doi:10.1007/s00439-019-02000-0 (2019). 44 Hayat, A., Umair, M., Abbas, S. et al. Identification of a novel biallelic missense variant in the KIAA0825 underlies postaxial polydactyly type A. Genomics 112, 2729-2733, doi:10.1016/j.ygeno.2020.03.006 (2020). 45 Li, J., Wei, J., Xu, P. et al. Impact of diabetes-related gene polymorphisms on the clinical characteristics of type 2 diabetes Chinese Han population. Oncotarget 7, 85464-85471, doi:10.18632/oncotarget.13399 (2016). 46 Huang, Y. C., Lin, J. M., Lin, H. J. et al. Genome-wide association study of diabetic retinopathy in a Taiwanese population. Ophthalmology 118, 642-648, doi:10.1016/j.ophtha.2010.07.020 (2011). 47 Cha, P. C., Zembutsu, H., Takahashi, A. et al. A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population. J Hum Genet 57, 235-237, doi:10.1038/jhg.2012.9 (2012). 48 Delgado, A. P., Brandao, P., Chapado, M. J. et al. Open reading frames associated with cancer in the dark matter of the human genome. Cancer Genomics Proteomics 11, 201-213 (2014). 49 Hsu, P. D., Lander, E. S. & Zhang, F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262-1278, doi:10.1016/j.cell.2014.05.010 (2014). 50 Doudna, J. A. & Charpentier, E. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096, doi:doi:10.1126/science.1258096 (2014). 51 Gasiunas, G., Barrangou, R., Horvath, P. et al. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A 109, E2579-2586, doi:10.1073/pnas.1208507109 (2012). 52 Jinek, M., Chylinski, K., Fonfara, I. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816-821, doi:10.1126/science.1225829 (2012). 53 Bibikova, M., Golic, M., Golic, K. G. et al. Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases. Genetics 161, 1169-1175 (2002). 54 Capecchi, M. R. Altering the genome by homologous recombination. Science 244, 1288-1292 (1989). 55 Labun, K., Montague, T. G., Krause, M. et al. CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing. Nucleic Acids Research 47, W171-W174, doi:10.1093/nar/gkz365 (2019). 56 Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat Methods 11, 783-784, doi:10.1038/nmeth.3047 (2014). 57 Shalem, O., Sanjana, N. E., Hartenian, E. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84-87, doi:10.1126/science.1247005 (2014). 58 Cowper-Sal lari, R., Zhang, X., Wright, J. B. et al. Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression. Nat Genet 44, 1191-1198, doi:10.1038/ng.2416 (2012). 59 Campbell, T. M., Castro, M. A. A., de Santiago, I. et al. FGFR2 risk SNPs confer breast cancer risk by augmenting oestrogen responsiveness. Carcinogenesis 37, 741-750, doi:10.1093/carcin/bgw065 (2016). 60 Zhang, X., Zhou, L., Fu, G. et al. The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis 35, 2062-2067, doi:10.1093/carcin/bgu103 (2014). 61 Lv, Z., Xu, Q. & Yuan, Y. A systematic review and meta-analysis of the association between long non-coding RNA polymorphisms and cancer risk. Mutat Res Rev Mutat Res 771, 1-14, doi:10.1016/j.mrrev.2016.10.002 (2017). 62 Visser, M., Palstra, R. J. & Kayser, M. Allele-specific transcriptional regulation of IRF4 in melanocytes is mediated by chromatin looping of the intronic rs12203592 enhancer to the IRF4 promoter. Hum Mol Genet 24, 2649-2661, doi:10.1093/hmg/ddv029 (2015). 63 Wright, J. B., Brown, S. J. & Cole, M. D. Upregulation of c-MYC in cis through a large chromatin loop linked to a cancer risk-associated single-nucleotide polymorphism in colorectal cancer cells. Mol Cell Biol 30, 1411-1420, doi:10.1128/mcb.01384-09 (2010). 64 Hu, B., Jin, J., Guo, A.-Y. et al. GSDS 2.0: an upgraded gene feature visualization server. Bioinformatics 31, 1296-1297, doi:10.1093/bioinformatics/btu817 (2014). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84483 | - |
| dc.description.abstract | 分枝桿菌在臨床上可分為三大類，分別是結核分枝桿菌、麻風分枝桿菌和非結核分枝桿菌 (NTM)。NTM是環境中普遍存在的微生物，尤其生長在水和土壤中。有些NTM，像鳥型分枝桿菌復合體 (MAC) 和膿腫分枝桿菌屬於伺機性病菌，可能會引起肺部疾病 (NTM-LD)。由於NTM和結核分枝桿菌具有相似的性質，過去經常被誤診為結核病。近年全球NTM-LD的發病率和患病率逐漸增加。此外，NTM對抗生素有極強的抗藥性且NTM-LD難以治療。因此，對NTM感染增加原因的研究開始備受重視。NTM-LD通常不會在人與人之間傳播，但患有潛在肺病、免疫系統低下以及停經後瘦弱的女性有較高的風險感染NTM。先前的研究也證實NTM-LD患者存在遺傳易感性。然而，目前仍不清楚與NTM-LD易感性相關的遺傳因素。本論文主要是透過比對NTM-LD患者和健康人的基因體序列來尋找特定基因上的單核苷酸多態性 (single nucleotide polymorphism, SNP) 作為生物標記，並進一步探討遺傳變異與 NTM 易感性之間的關聯，從而提升NTM-LD的初步診斷與預防。我們透過全基因組關聯分析 (GWAS) 在兩組基因體序列之間發現有20個顯著差異的SNPs坐落於KIAA0825基因中。KIAA0825的已知主要產物有長、短兩個異構體，但功能仍未知。我們發現在病患檢體中長異構體的比例比健康控制組多，此外我們建立了CRISPR/Cas9的基因剔除系統並運用在巨噬細胞中，我們觀察到當THP1細胞株的KIAA0825基因剔除或是突變後，受刺激細胞的生長速度會受到影響，透過實驗我們發現KIAA0825基因可能扮演重要的角色來影響台灣人對NTM的遺傳易感性。儘管 KIAA0825 基因產物的功能尚不清楚，但經由分析主要長短兩種亞型 mRNA 的表現量，發現 KIAA0825 在 MAC-LD 患者中的長亞型比例較高。此外，也藉由 CRISPR/Cas9 基因組編輯系統建構了具有長亞型KIAA0825-基因剔除及全KIAA0825-基因剔除的 THP1 單核球細胞株。我們進一步證明，具有長亞型 KIAA0825-基因剔除或全 KIAA0825-基因剔除的 THP1 細胞生長速率會受到影響。這表明 KIAA0825 基因可能在巨噬細胞中發揮重要作用，使細胞在發炎和感染期間能維持其活力。 | zh_TW |
| dc.description.abstract | Mycobacteria are a family of rod-shaped bacilli that are clinically classified into three major groups, including Mycobacterium tuberculosis, Mycobacterium leprae and Nontuberculous mycobacteria (NTM). NTM are ubiquitous in the environment and especially exist in water source and soil. Some NTM species, like Mycobacterium avium complex (MAC) and Mycobacterium abscessus, are pathogenic and would cause clinical diseases. NTM-lung disease (LD), the most common disease resulted from NTM infection, was often misdiagnosed as tuberculosis in the past due to the similar properties between NTM and M. tuberculosis. Recently, the incidence and prevalence of NTM-LD is increasing globally. Besides, NTM are extremely antibiotic resistant, and the disease is difficult to treat. Therefore, the reasons for the NTM increase are being elucidated in recent years. NTM-LD is typically not transmitted person-to-person, but people with underlying lung disease or depressed immune systems and thin women after menopause have a higher risk of NTM infection. The previous studies indicated that there are genetic predispositions in NTM-LD patients; however, genetic factors related to the NTM-LD susceptibility are still unclear. This study aims to identify specific single nucleotide polymorphisms (SNPs) on specific genes as biomarkers by comparing the gene sequences of NTM-LD patients and healthy people, and further to clarify the association between genetic variants and NTM susceptibility that could improve preliminary diagnosis and prevention for NTM-LD. Based on a genome-wide association study (GWAS) analysis, 20 SNPs on the KIAA0825 gene with significant differences between two groups have been identified. Although the function of KIAA0825 gene-encoded products is still unclear, we analyzed the mRNA expression of the major long and short isoforms and demonstrated that the long isoform proportion of KIAA0825 in MAC-LD patients was higher. In addition, THP1 monocytic leukemia cell lines with the long isoform KIAA0825-knockout or full KIAA0825-knockout have been established via a CRISPR/Cas9 genome editing system. We further demonstrated that the growth rate of the stimulated THP1 cell clones with the long isoform KIAA0825-knockout or full KIAA0825-knockout was affected. It suggests that the KIAA0825 gene may play an important role in macrophages to maintain their viability during inflammation and infection. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:13:02Z (GMT). No. of bitstreams: 1 U0001-2309202215394200.pdf: 4565946 bytes, checksum: d65cdf144aa428e9af520df9d4053e5f (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 誌謝 i 摘要 ii Abstract iv 圖目錄 ix 表目錄 x Chapter 1 緒論 (Introduction) 1 1.1 非結核分枝桿菌 (Nontuberculous mycobacteria, NTM) 1 1.1.1 分枝桿菌的分類 (Class of mycobacteria) 1 1.1.2 NTM的感染 (NTM infection) 1 1.1.3 NTM的發病機制 (Pathogenesis of NTM) 2 1.1.4 NTM的易感性 (Susceptibility of NTM) 2 1.2 單核苷酸多態性 (Single nucleotide polymorphism, SNP) 3 1.3 全基因組關聯分析 (Genome-wide association study) 4 1.4 非結合分枝桿菌感染與單核苷酸多態性 (NTM infection and SNP) 4 1.5 KIAA0825基因 (KIAA0825 gene) 5 1.5.1 KIAA基因家族 (Kazusa ORFeome Project) 5 1.5.2 KIAA0825基因結構與功能 (Gene structure and function) 6 1.6 CRISPR/Cas9基因剔除 (CRISPR/Cas9 gene knockout) 6 1.7 研究目標 (Specific aim) 7 Chapter 2 材料與方法 (Materials and methods) 9 2.1 細胞培養 (Cell culture) 9 2.2 質體 (Plasmids) 9 2.2.1 LentiCRISPRv2-IRES-GFP質體 9 2.2.2 LentiCRISPRv2-2A-GFP-Puro質體 9 2.2.3 gRNA序列接入LentiCRISPRv2質體 10 2.2.4 pcDNA-3FLAG-KIAA0825質體 10 2.2.5 pHAGE-TRE-KIAA0825-IRES-dsRED-UBC-rtTA-T2A-GFP質體 10 2.3 DNA轉型作用 (DNA transformation) 11 2.4 質體DNA萃取 (Plasmid DNA extraction) 11 2.5 慢病毒轉導與細胞克隆 (Lentivirus transduction and cell clone) 11 2.6 質體DNA轉染 (Plasmid DNA transfection) 12 2.7 mRNA萃取與反轉錄聚合酶連鎖反應 (mRNA isolation and reverse transcription-PCR) 12 2.8 即時定量聚合酶連鎖反應 (Real-time quantitative PCR) 13 2.9 西方墨點法 (Western blot) 13 2.10 基因體DNA萃取 (Genomic DNA extraction) 14 2.11 DNA定序 (DNA sequencing) 14 2.12 細胞存活率分析 (Survival analysis) 14 2.12.1 MTT 試驗 14 2.12.2 WST-1試驗 15 2.13 全基因組關聯分析 (Genome-wide association study) 15 2.14 統計分析 (Statistical analysis) 15 Chapter 3 結果 (Results) 16 3.1 GWAS分析中發現有20個SNPs位於KIAA0825基因 16 3.2 病患及健康控制組中KIAA0825 mRNA的表現量 16 3.2.1 KIAA0825基因結構 16 3.2.2 檢體KIAA0825 mRNA的表現量 17 3.3 利用CRISPR/Cas9建構KIAA0825基因剔除系統 18 3.3.1 gRNA設計 18 3.3.2 LentiCRISPRv2-IRES-GFP質體建構 19 3.3.3 LentiCRISPRv2-2A-GFP-Puro質體建構 19 3.4 建立KIAA0825基因剔除THP1細胞 20 3.4.1 生產帶有LentiCRISPRv2 sgRNA質體的慢病毒 20 3.4.2 慢病毒感染THP1細胞 20 3.4.3 挑選KIAA0825基因剔除的單一細胞株THP1細胞 21 3.5 THP1剔除KIAA0825基因的影響 21 3.5.1 短時間刺激物作用後生長分析 21 3.5.2 長時間持續刺激下的生長變化 22 Chapter 4 討論 (Discussion) 23 4.1 由GWAS結果找到可能的差異基因 23 4.2 剔除KIAA0825對THP1的影響 24 4.3 過表達KIAA0825對THP1的影響 26 4.4 在其他細胞中觀察KIAA0825的機制 27 4.5 SNPs在KIAA0825基因中扮演的角色 27 Chapter 5 參考資料 (References) 29 Chapter 6 附圖 (Figures) 35 Chapter 7 圖表 (Tables) 55 | |
| dc.language.iso | zh-TW | |
| dc.title | 台灣人口中非結核分枝桿菌肺病的全基因組關聯分析 | zh_TW |
| dc.title | Genome-wide association study of non-tuberculous mycobacterial lung disease in Taiwanese population | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 詹世鵬(Shih-Peng chan),樹金忠(Chin-Chung Shu) | |
| dc.subject.keyword | 非結合分枝桿菌,遺傳易感性,單核苷酸多態性,全基因組關聯分析,KIAA0825,CRISPR/Cas9剔除系統, | zh_TW |
| dc.subject.keyword | Nontuberculous mycobacteria (NTM),Genetic predisposition,Single nucleotide polymorphisms (SNPs),Genome-wide association study (GWAS),KIAA0825,CRISPR/Cas9 knockout, | en |
| dc.relation.page | 61 | |
| dc.identifier.doi | 10.6342/NTU202203920 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-09-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2022-10-13 | - |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2309202215394200.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 4.46 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。