請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37283完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳為堅(Wen-Jen Chen) | |
| dc.contributor.author | Chi-Yu Lai | en |
| dc.contributor.author | 賴季侑 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:23:20Z | - |
| dc.date.available | 2013-08-08 | |
| dc.date.copyright | 2008-08-08 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-22 | |
| dc.identifier.citation | Abelson, J.F., Kwan, K.Y., O'Roak, B.J., Baek, D.Y., Stillman, A.A., Morgan, T.M., Mathews, C.A., Pauls, D.L., Rasin, M.R., Gunel, M., et al. (2005). Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317-320.
American Psychological Association (2000). Diagnostic and Statistical Manual of Mental Disorders (4th ed. Text Revision). Washington, DC: Author. Austin, J., Buckland, P., Cardno, A.G., Williams, N., Spurlock, G., Hoogendoorn, B., Zammit, S., Jones, G., Sanders, R., Jones, L., et al. (2000). The high affinity neurotensin receptor gene (NTSR1): comparative sequencing and association studies in schizophrenia. Mol Psychiatry 5, 552-557. Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297. Bassett, A.S., Chow, E.W., AbdelMalik, P., Gheorghiu, M., Husted, J., and Weksberg, R. (2003). The schizophrenia phenotype in 22q11 deletion syndrome. Am J Psychiatry 160, 1580-1586. Betel, D., Wilson, M., Gabow, A., Marks, D.S., and Sander, C. (2008). The microRNA.org resource: targets and expression. Nucleic Acids Res 36, D149-153. Bilkei-Gorzo, A., Racz, I., Michel, K., and Zimmer, A. (2002). Diminished anxiety- and depression-related behaviors in mice with selective deletion of the Tac1 gene. J Neurosci 22, 10046-10052. Bray, N.J., and Owen, M.J. (2001). Searching for schizophrenia genes. Trends Mol Med 7, 169-174. Calin, G.A., and Croce, C.M. (2006). MicroRNA signatures in human cancers. Nat Rev Cancer 6, 857-866. Chen, C.H. (2002). Generalized association plots: Information visualization via iteratively generated correlation matrices. Stat Sin 12, 7-29. Chen, C.Z. (2005). MicroRNAs as oncogenes and tumor suppressors. N Engl J Med 353, 1768-1771. Chen, H.Y., Yu, S.L., Chen, C.H., Chang, G.C., Chen, C.Y., Yuan, A., Cheng, C.L., Wang, C.H., Terng, H.J., Kao, S.F., et al. (2007). A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 356, 11-20. Chen, W.J., Liu, S.K., Chang, C.J., Lien, Y.J., Chang, Y.H., and Hwu, H.G. (1998). Sustained attention deficit and schizotypal personality features in nonpsychotic relatives of schizophrenic patients. Am J Psychiatry 155, 1214-1220. Chien, I.C., Chou, Y.J., Lin, C.H., Bih, S.H., Chou, P., and Chang, H.J. (2004). Prevalence and incidence of schizophrenia among national health insurance enrollees in Taiwan, 1996-2001. Psychiatry Clin Neurosci 58, 611-618. Compton, W.M., 3rd, Helzer, J.E., Hwu, H.G., Yeh, E.K., McEvoy, L., Tipp, J.E., and Spitznagel, E.L. (1991). New methods in cross-cultural psychiatry: psychiatric illness in Taiwan and the United States. Am J Psychiatry 148, 1697-1704. Crow, T.J. (2007). How and why genetic linkage has not solved the problem of psychosis: review and hypothesis. Am J Psychiatry 164, 13-21. Debbane, M., Glaser, B., David, M.K., Feinstein, C., and Eliez, S. (2006). Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: Neuropsychological and behavioral implications. Schizophr Res 84, 187-193. Freeman, W.M., Walker, S.J., and Vrana, K.E. (1999). Quantitative RT-PCR: pitfalls and potential. Biotechniques 26, 112-122, 124-115. Gladkevich, A., Kauffman, H.F., and Korf, J. (2004). Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 28, 559-576. Glatt, S.J., Everall, I.P., Kremen, W.S., Corbeil, J., Sasik, R., Khanlou, N., Han, M., Liew, C.C., and Tsuang, M.T. (2005). Comparative gene expression analysis of blood and brain provides concurrent validation of SELENBP1 up-regulation in schizophrenia. Proc Natl Acad Sci USA 102, 15533-15538. Haag, A.L. (2007). Biomarkers trump behavior in mental illness diagnosis. Nat Med 13, 3. Hammond, S.M. (2006). MicroRNA therapeutics: a new niche for antisense nucleic acids. Trends Mol Med 12, 99-101. Hansen, T., Olsen, L., Lindow, M., Jakobsen, K.D., Ullum, H., Jonsson, E., Andreassen, O.A., Djurovic, S., Melle, I., Agartz, I., et al. (2007). Brain expressed microRNAs implicated in schizophrenia etiology. PLoS ONE 2, e873. Harrison, P.J., and Weinberger, D.R. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10, 40-68; image 45. Hastie, T., Tibshirani, R., and Friedman, J. (2001). The Elements of Statistical Learning: Data Mining, Inference, and Prediction (Springer). Hebert, S.S., and De Strooper, B. (2007). Molecular biology. miRNAs in neurodegeneration. Science 317, 1179-1180. Hebert, S.S., Horre, K., Nicolai, L., Papadopoulou, A.S., Mandemakers, W., Silahtaroglu, A.N., Kauppinen, S., Delacourte, A., and De Strooper, B. (2008). Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci USA 105, 6415-6420. Hsu, S.D., Chu, C.H., Tsou, A.P., Chen, S.J., Chen, H.C., Hsu, P.W., Wong, Y.H., Chen, Y.H., Chen, G.H., and Huang, H.D. (2008). miRNAMap 2.0: genomic maps of microRNAs in metazoan genomes. Nucleic Acids Res 36, D165-169. Jablensky, A. (2000). Epidemiology of schizophrenia: the global burden of disease and disability. Eur Arch Psychiatry Clin Neurosci 250, 274-285. Jarskog, L.F., Miyamoto, S., and Lieberman, J.A. (2007). Schizophrenia: new pathological insights and therapies. Annu Rev Med 58, 49-61. Jin, P., Alisch, R.S., and Warren, S.T. (2004). RNA and microRNAs in fragile X mental retardation. Nat Cell Biol 6, 1048-1053. Kim, J., Krichevsky, A., Grad, Y., Hayes, G.D., Kosik, K.S., Church, G.M., and Ruvkun, G. (2004). Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci USA 101, 360-365. Kiriakidou, M., Nelson, P.T., Kouranov, A., Fitziev, P., Bouyioukos, C., Mourelatos, Z., and Hatzigeorgiou, A. (2004). A combined computational-experimental approach predicts human microRNA targets. Genes Dev 18, 1165-1178. Krek, A., Grun, D., Poy, M.N., Wolf, R., Rosenberg, L., Epstein, E.J., MacMenamin, P., da Piedade, I., Gunsalus, K.C., Stoffel, M., et al. (2005). Combinatorial microRNA target predictions. Nat Genet 37, 495-500. Lewis, B.P., Burge, C.B., and Bartel, D.P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20. Lewis, D.A. (2002). In pursuit of the pathogenesis and pathophysiology of schizophrenia: where do we stand? American Journal of Psychiatry 159, 1467-1469. Lieberman, J.A., Perkins, D.O., and Jarskog, L.F. (2007). Neuroprotection: a therapeutic strategy to prevent deterioration associated with schizophrenia. CNS Spectr 12, 1-13; quiz 14. Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B.L., Mak, R.H., Ferrando, A.A., et al. (2005). MicroRNA expression profiles classify human cancers. Nature 435, 834-838. Middleton, F.A., Pato, C.N., Gentile, K.L., McGann, L., Brown, A.M., Trauzzi, M., Diab, H., Morley, C.P., Medeiros, H., Macedo, A., et al. (2005). Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches. Am J Med Genet B Neuropsychiatr Genet 136, 12-25. Moises, H.W., Zoega, T., and Gottesman, II (2002). The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia. BMC Psychiatry 2, 8. Monteiro, M.G. (2001). A World Health Organization perspective on alcohol and illicit drug use and health. Eur Addict Res 7, 98-103. Nurnberger, J.I., Jr., Blehar, M.C., Kaufmann, C.A., York-Cooler, C., Simpson, S.G., Harkavy-Friedman, J., Severe, J.B., Malaspina, D., and Reich, T. (1994). Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry 51, 849-859. Perkins, D.O., Jeffries, C., and Sullivan, P. (2005). Expanding the 'central dogma': the regulatory role of nonprotein coding genes and implications for the genetic liability to schizophrenia. Mol Psychiatry 10, 69-78. Perkins, D.O., Jeffries, C.D., Jarskog, L.F., Thomson, J.M., Woods, K., Newman, M.A., Parker, J.S., Jin, J., and Hammond, S.M. (2007). microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 8, R27. Picchioni, M.M., and Murray, R.M. (2007). Schizophrenia. BMJ 335, 91-95. Quackenbush, J. (2006). Microarray analysis and tumor classification. N Engl J Med 354, 2463-2472. Ray, S., Britschgi, M., Herbert, C., Takeda-Uchimura, Y., Boxer, A., Blennow, K., Friedman, L.F., Galasko, D.R., Jutel, M., Karydas, A., et al. (2007). Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med 13, 1359-1362. Risch, N. (1990). Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 46, 222-228. Rogaev, E.I. (2005). Small RNAs in human brain development and disorders. Biochemistry (Mosc) 70, 1404-1407. Saha, S., Chant, D., Welham, J., and McGrath, J. (2005). A systematic review of the prevalence of schizophrenia. PLoS Med 2, e141. Seeman, M.V. (1996). The role of estrogen in schizophrenia. J Psychiatry Neurosci 21, 123-127. Simon, R., Radmacher, M.D., Dobbin, K., and McShane, L.M. (2003). Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification. J Natl Cancer Inst 95, 14-18. Sullivan, P.F., Fan, C., and Perou, C.M. (2006). Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 141, 261-268. Tsuang, M. (2000). Schizophrenia: genes and environment. Biol Psychiatry 47, 210-220. Tsuang, M.T., Nossova, N., Yager, T., Tsuang, M.M., Guo, S.C., Shyu, K.G., Glatt, S.J., and Liew, C.C. (2005). Assessing the validity of blood-based gene expression profiles for the classification of schizophrenia and bipolar disorder: a preliminary report. Am J Med Genet B Neuropsychiatr Genet 133, 1-5. Vapnik, V.N. (2000). The Nature of Statistical Learning Theory (Springer). Vawter, M.P., Ferran, E., Galke, B., Cooper, K., Bunney, W.E., and Byerley, W. (2004). Microarray screening of lymphocyte gene expression differences in a multiplex schizophrenia pedigree. Schizophr Res 67, 41-52. Wang, X. (2006). Systematic identification of microRNA functions by combining target prediction and expression profiling. Nucleic Acids Res 34, 1646-1652. Yao, Y., Schroder, J., and Karlsson, H. (2007). Verification of proposed peripheral biomarkers in mononuclear cells of individuals with schizophrenia. J Psychiatr Res. Yu, S.L., Chen, H.Y., Chang, G.C., Chen, C.Y., Chen, H.W., Singh, S., Cheng, C.L., Yu, C.J., Lee, Y.C., Chen, H.S., et al. (2008). MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 13, 48-57. Zhang, C., Fu, H., Jiang, Y., and Yu, T. (2007). High-dimensional pseudo-logistic regression and classification with applications to gene expression data. Comput Stat Data Anal 52, 452-470. Zhang, D., Sliwkowski, M.X., Mark, M., Frantz, G., Akita, R., Sun, Y., Hillan, K., Crowley, C., Brush, J., and Godowski, P.J. (1997). Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4. Proc Natl Acad Sci USA 94, 9562-9567. Zvara, A., Szekeres, G., Janka, Z., Kelemen, J.Z., Cimmer, C., Santha, M., and Puskas, L.G. (2005). Over-expression of dopamine D2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers. Dis Markers 21, 61-69. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37283 | - |
| dc.description.abstract | 最近陸續有研究顯示周邊血液的基因表現某種程度可以區分精神分裂症疾病狀態，有潛力用來作為精神分裂症診斷的工具，但至目前為止周邊血液基因表現研究都局限於訊息核醣核酸 (mRNAs) 的探索。最近，微小核醣核酸 (microRNAs) 逐漸被證實是調控神經發育與功能的重要分子，或許周邊血液的微小核醣核酸表現剪影具有潛力發展為精神分裂症生物標記。本研究嘗試自周邊血液尋找特定的微小核醣核酸，發展精神分裂症之生物標記。研究擬自台大醫院收集20位精神分裂症病人與20位性別年齡配對的健康對照。利用ABI PRISM 7900即時反轉錄聚合酶連鎖反應 (real time RT-PCR) 方法測量365種人類微小核醣核酸的表現。我們使用監督性分類 (supervised classification)，並進行交叉驗證 (cross-validation) 來選擇具分類代表性的微小核醣核酸。接著使用生物資訊的方法，預測這些微小核醣核酸調控的基因群，以及生物功能。本研究定義6個微小核醣核酸標誌，可以將精神分裂症與健康對照區分 (準確率70-80%)。而這些微小核醣核酸標誌可能參與雌激素訊息傳導與多巴胺訊息傳導途徑，且與神經以及骨骼與肌肉發育與功能相關。結果顯示以血液中的全基因體微小核醣核酸表現剪影定義精神分裂症的生物標記是可行的，本研究定義的6個微小核醣核酸標誌將進行進一步探究。 | zh_TW |
| dc.description.abstract | Recently several studies have demonstrated the potential utility of the blood-based gene expression profiling as a diagnostic tool for schizophrenia, though these studies were limited to the expression of protein-coding genes. The expressions of non-coding genes such as microRNAs (miRNAs) are now considered to play a significant role for the regulation of gene expression by means of inhibiting the translation of messenger RNAs (mRNAs), indicating that the miRNAs profiling in the peripheral blood might be potential biomarkers for schizophrenia. This study aimed to identify blood-based miRNA signature and evaluate its potential as biomarkers for schizophrenia. The study enrolled 20 schizophrenia patients at National Taiwan University Hospital and 20 age- and gender-matched normal controls. The expressions of 368 human miRNAs in their peripheral blood were examined using ABI PRISM 7900 Real Time PCR system. Supervised classification with internal cross-validation method was used to identify miRNAs that might be useful as biomarkers for schizophrenia. Possible biological mechanisms implicated in the target genes involved by the miRNAs were explored using bioinformatic methods as well. We identified a blood-based six-miRNA signature that could discriminate schizophrenia patients from normal controls with an accuracy rate ranging from 70% to 80%. Bioinformatic analyses indicated that dysregulation of these miRNAs in peripheral blood might be involved in estrogen receptor and dopamine receptor signaling pathways in schizophrenia patients. Moreover, possible biological functions of the target genes regulated by the six miRNAs included nervous, skeletal, and muscular system development and function. We concluded that genome-wide miRNA profiling was a feasible way for the identification of biomarkers for schizophrenia and the six-miRNA signature identified in this study warrants further investigation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:23:20Z (GMT). No. of bitstreams: 1 ntu-97-R95842003-1.pdf: 961857 bytes, checksum: d60670330797864a34537bc65effd7de (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 誌 謝 I
中文摘要 II ABSTRACT III CONTENT IV LIST OF TABLES VI LIST OF FIGURES VI LIST OF APPENDIXES VI 1. Introduction 1 1.1 Schizophrenia and its genetic basis 1 1.2 Blood-based gene expression biomarkers for schizophrenia 2 1.3 MicroRNAs (miRNAs) and schizophrenia 4 1.4 Specific aims 6 2. Methods 7 2.1 Study subjects 7 2.2 Measurements 7 2.3 RNA extraction 7 2.4 MiRNA profiling 8 2.5 Statistic analysis 8 2.5.1 Features selection 8 2.5.2 Supervised classification and cross-validation 9 2.5.3 Cluster analysis for subclass discovery of patients with schizophrenia 10 2.5.4 Target genes prediction and functional profiling 10 3. Results 12 4. Discussion 14 4.1 Supervised classification with leave-one-out cross-validation 14 4.2 Six-miRNA signature and its implicated biological functions 15 4.3 Limitations 17 4.4 Conclusions 17 5. References 19 6. Appendixes 37 | |
| dc.language.iso | en | |
| dc.title | 精神分裂症之潛在生物標記探索：微小核醣核酸在周邊血液表現分析 | zh_TW |
| dc.title | MicroRNA profiles in peripheral blood as potential biomarkers for schizophrenia | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 胡海國(Hai-Gwo Hwu),孫孝芳(Hsiao-Fang Sunny Sun),李文宗(Wen-Chung Li),陳璿宇(Hsuan-Yu Chen) | |
| dc.subject.keyword | 精神分裂症,生物標誌,周邊血液組織,基因表現剪影,微小核醣核酸, | zh_TW |
| dc.subject.keyword | schizophrenia,peripheral blood,gene expression profiling,microRNA, | en |
| dc.relation.page | 40 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-23 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-97-1.pdf 目前未授權公開取用 | 939.31 kB | Adobe PDF |
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。