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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳為堅 | |
| dc.contributor.author | Yu-Shan Chou | en |
| dc.contributor.author | 周佑珊 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:15:15Z | - |
| dc.date.available | 2015-09-24 | |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-19 | |
| dc.identifier.citation | Bartel, D. P. 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
Beveridge, N. J., Gardiner E., Carroll A. P., Tooney P. A. & Cairns M. J. 2010. Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry, 15, 1176-89. Burmistrova, O. A., Goltsov A. Y., Abramova L. I., Kaleda V. G., Orlova V. A. & Rogaev E. I. 2007. MicroRNA in schizophrenia: Genetic and expression analysis of miR-130b (22q11). Biochemistry (Moscow), 72, 578-582. Chen, W. J., Liu S. K., Chang C. J., Lien Y. J., Chang Y. H. & Hwu H. G. 1998. Sustained attention deficit and schizotypal personality features in nonpsychotic relatives of schizophrenic patients. Am J Psychiatry, 155, 1214-20. Feng, J., Sun G., Yan J., Noltner K., Li W., Buzin C. H., Longmate J., Heston L. L., Rossi J. & Sommer S. S. 2009. Evidence for X-chromosomal schizophrenia associated with microRNA alterations. PLoS One, 4, e6121. Freedman, R. 2003. Schizophrenia. N Engl J Med, 349, 1738-49. Gardiner, E., Beveridge N. J., Wu J. Q., Carr V., Scott R. J., Tooney P. A. & Cairns M. J. 2012. Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells. Mol Psychiatry, 17, 827-40. Gong, J., Tong Y., Zhang H. M., Wang K., Hu T., Shan G., Sun J. & Guo A. Y. 2012. Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum Mutat, 33, 254-63. Griffiths-Jones, S., Saini H. K., Van Dongen S. & Enright A. J. 2008. miRBase: tools for microRNA genomics. Nucleic Acids Res, 36, D154-8. Kim, V. N. & Nam J. W. 2006. Genomics of microRNA. Trends Genet, 22, 165-73. Klein, M. E., Impey S. & Goodman R. H. 2005. Role reversal: the regulation of neuronal gene expression by microRNAs. Curr Opin Neurobiol, 15, 507-13. Lai, C. Y., Yu S. L., Hsieh M. H., Chen C. H., Chen H. Y., Wen C. C., Huang Y. H., Hsiao P. C., Hsiao C. K., Liu C. M., et al. 2011. MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia. PLoS One, 6, e21635. Lee, H. Y. & Doudna J. A. 2012. TRBP alters human precursor microRNA processing in vitro. RNA, 18, 2012-9. Lin, D. Y., Zeng D. & Millikan R. 2005. Maximum likelihood estimation of haplotype effects and haplotype-environment interactions in association studies. Genet Epidemiol, 29, 299-312. Nurnberger, J. I., Jr., Blehar M. C., Kaufmann C. A., York-Cooler C., Simpson S. G., Harkavy-Friedman J., Severe J. B., Malaspina D. & Reich T. 1994. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry, 51, 849-59; discussion 863-4. Obernosterer, G., Leuschner P. J., Alenius M. & Martinez J. 2006. Post-transcriptional regulation of microRNA expression. RNA, 12, 1161-7. Perkins, D. O., Jeffries C. D., Jarskog L. F., Thomson J. M., Woods K., Newman M. A., Parker J. S., Jin J. & Hammond S. M. 2007. microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol, 8, R27. Ripke, S., Sanders A. R., Kendler K. S., Levinson D. F., Sklar P., Holmans P. A., Lin D. Y., Duan J., Ophoff R. A., Andreassen O. A., et al. 2011. Genome-wide association study identifies five new schizophrenia loci. Nat Genet, 43, 969-76. Ryan, B. M., Robles A. I. & Harris C. C. 2010. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer, 10, 389-402. Saha, S., Chant D. & Mcgrath J. 2008. Meta-analyses of the incidence and prevalence of schizophrenia: conceptual and methodological issues. Int J Methods Psychiatr Res, 17, 55-61. Saini, H. K., Enright A. J. & Griffiths-Jones S. 2008. Annotation of mammalian primary microRNAs. BMC Genomics, 9, 564. Saini, H. K., Griffiths-Jones S. & Enright A. J. 2007. Genomic analysis of human microRNA transcripts. Proc Natl Acad Sci U S A, 104, 17719-24. Santarelli, D. M., Beveridge N. J., Tooney P. A. & Cairns M. J. 2011. Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia. Biol Psychiatry, 69, 180-7. Schmittgen, T. D., Lee E. J., Jiang J., Sarkar A., Yang L., Elton T. S. & Chen C. 2008. Real-time PCR quantification of precursor and mature microRNA. Methods, 44, 31-8. Sun, G., Yan J., Noltner K., Feng J., Li H., Sarkis D. A., Sommer S. S. & Rossi J. J. 2009. SNPs in human miRNA genes affect biogenesis and function. RNA, 15, 1640-51. Tamminga, C. A. & Holcomb H. H. 2005. Phenotype of schizophrenia: a review and formulation. Mol Psychiatry, 10, 27-39. Thomson, J. M. 2006. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes & Development, 20, 2202-2207. Tiwari, A. K., Zai C. C., Muller D. J. & Kennedy J. L. 2010. Genetics in schizophrenia: where are we and what next? Dialogues Clin Neurosci, 12, 289-303. Tran, N. & Hutvagner G. 2013. Biogenesis and the regulation of the maturation of miRNAs. Essays Biochem, 54, 17-28. Xu, Y., Li F., Zhang B., Zhang K., Zhang F., Huang X., Sun N., Ren Y., Sui M. & Liu P. 2010. MicroRNAs and target site screening reveals a pre-microRNA-30e variant associated with schizophrenia. Schizophr Res, 119, 219-27. Zhang, J., Wheeler D. A., Yakub I., Wei S., Sood R., Rowe W., Liu P. P., Gibbs R. A. & Buetow K. H. 2005. SNPdetector: a software tool for sensitive and accurate SNP detection. PLoS Comput Biol, 1, e53. Zhou, Y., Wang J., Lu X., Song X., Ye Y., Zhou J., Ying B. & Wang L. 2013. Evaluation of six SNPs of MicroRNA machinery genes and risk of schizophrenia. J Mol Neurosci, 49, 594-9. Zou, M., Li D., Lv R., Zhou Y., Wang T., Liu J., Tao C., Ying B. & Wang L. 2012. Association between two single nucleotide polymorphisms at corresponding microRNA and schizophrenia in a Chinese population. Mol Biol Rep, 39, 3385-91. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60308 | - |
| dc.description.abstract | 微小核醣核酸 (microRNA) 為一重要的基因表現調控因子，其表現量可能在許多疾病中扮演重要角色。另外，許多文獻指出，微小核醣核酸基因上的單一核苷酸多型性 (single nucleotide polymorphism)，為影響其表現量的因素之一。在之前研究中，有兩個微小核醣核酸基因miR-34a與miR-432的表現量，顯著在精神分裂症病人跟健康對照組身上有差異。故本研究欲探討此兩個候選基因上的單一核苷酸多型性與精神分裂症之相關性，以及這些單一核苷酸多型性與微小核醣核酸表現量的關聯性。研究樣本來自2007至2009年收案的90名台大醫院精神分裂症病人及60名健康對照。收集其周邊血液後，針對兩個候選基因，在其先驅微小核糖核酸 (precursor miRNA) 序列上下500個核苷酸的範圍，使用ABI 3730做定序。在微小核糖核酸表現量部分，則使用ABI 7900即時反轉錄聚合酶連鎖反應 (real-time RT-PCR) 測得。定序後，在我們的樣本中找到6個變異，包括在miR-432基因上的2個已知的單一核苷酸多型性，以及在miR-34a基因上的4個新變異。在單一核苷酸多型性之基因型跟疾病狀態相關性的分析中，雖然都未達到顯著相關性，但仍可看出在rs41286564，精神分裂症病人帶有較多的C對偶基因。在單一核苷酸多型性rs41286564基因型與微小核糖核酸表現量的分析，雖然仍未達到顯著差異的結果，但在精神分裂症病人中可觀察到帶有G對偶基因者，有較低miR-432表現量的趨勢存在。在有限的結果下，小樣本的研究仍提供一些在微小核糖核酸基因上的單一核苷酸多型性與精神分裂症間的線索，未來可用更全面的方式進一步探究微小核糖核酸基因在精神分裂症病因扮演的角色。 | zh_TW |
| dc.description.abstract | Recent studies have indicated aberrant microRNA (miRNA) expressions detected from both the blood and brains are associated with schizophrenia. Single nucleotide polymorphisms (SNPs) located at miRNA genes were linked to different levels of miRNA expression. Some studies suggested that genetic variants around miRNA genes miR-34a and miR-432 were associated with schizophrenia. This study aimed to investigate whether SNPs within two candidate miRNA genes are associated with schizophrenia, and explore the correlation between such SNP and the expression level of the corresponding miRNA. Participants consisted of 90 schizophrenia patients recruited from National Taiwan University Hospital and 60 healthy controls from university staffs, students, and community volunteers during 2007-2009. Their venous blood was collected for DNA extraction. Sequencing was used to search for variants within the segment of +/- 500 bp of precursor miRNA genes (pre-miRNAs). In addition, the total RNA was extracted from mononuclear leukocytes. The corresponding cDNAs were obtained by reverse transcription PCR and the RNA expression levels were measured using quantitative real-time PCR. There were 6 variants indicated after screening. Two in miR-432 gene had been reported as SNPs (rs185297997 and rs41286564), and the rest in miR-34a were novel variants. Genetic association analysis showed no statistically significant association between any miRNA SNPs and schizophrenia though higher frequency of C allele of SNP rs41286564 in schizophrenia patients was revealed. In correlation analysis, there was no significant result though the effect of G allele was presented to reduce miR-432 expression level in schizophrenia patients. Further convergent analysis for miRNA biogenesis should be tested in investigating the etiology of schizophrenia. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:15:15Z (GMT). No. of bitstreams: 1 ntu-102-R00849022-1.pdf: 1184988 bytes, checksum: 64289dda444409886ab76999a3326de6 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii 1. Introduction 1 1.1 Schizophrenia and its genetic basis 1 1.2 MicroRNAs and schizophrenia 1 1.3 Single nucleotide polymorphisms within miRNA genes 2 1.4 Specific aims 3 2. Materials and methods 5 2.1 Subjects 5 2.2 Measurements 5 2.3 Selection of miRNAs 5 2.4 DNA extraction and sequencing 6 2.5 RNA extraction and miRNA quantification 7 2.6 Statistical analysis 8 3. Results 9 3.1 Demographic characteristics 9 3.2 Genetic variants of miRNAs 9 3.3 Association analysis 10 3.4 SNP rs41286564 genotype and miR432 expression level 11 4. Discussion 13 4.1 Association between miRNA SNPs and schizophrenia 13 4.2 Correlation of miRNA genotype and expression levels 14 4.3 Limitation 14 4.4 Conclusion 15 5. References 16 6. Appendices 28 | |
| dc.language.iso | en | |
| dc.subject | 生成過程 | zh_TW |
| dc.subject | 單一核苷 | zh_TW |
| dc.subject | 酸多型性 | zh_TW |
| dc.subject | 微小核糖核酸 | zh_TW |
| dc.subject | 精神分裂症 | zh_TW |
| dc.subject | schizophrenia | en |
| dc.subject | microRNA | en |
| dc.subject | biogenesis | en |
| dc.subject | SNPs | en |
| dc.title | 微小核醣核酸基因miR-34a和miR-432上單一核苷酸多型性與精神分裂症之相關性研究 | zh_TW |
| dc.title | Relations of Genetic Polymorphisms in MicroRNA Genes miR-34a and miR-432 to Schizophrenia | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 俞松良,郭柏秀,劉智民 | |
| dc.subject.keyword | 精神分裂症,微小核糖核酸,生成過程,單一核苷,酸多型性, | zh_TW |
| dc.subject.keyword | schizophrenia,microRNA,biogenesis,SNPs, | en |
| dc.relation.page | 30 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-19 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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