請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66197
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 賴亮全(Liang-Chuan Lai) | |
dc.contributor.author | Yi-Yu Su | en |
dc.contributor.author | 蘇怡羽 | zh_TW |
dc.date.accessioned | 2021-06-17T00:25:15Z | - |
dc.date.available | 2017-09-19 | |
dc.date.copyright | 2012-09-19 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-03-30 | |
dc.identifier.citation | 1. Reznik, A.G., [Morphology of acute myocardial infarction at prenecrotic stage]. Kardiologiia, 2010. 50(1): p. 4-8.
2. Fuster, V., et al., ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation, 2006. 114(7): p. e257-354. 3. Martini, B., et al., Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J, 1989. 118(6): p. 1203-9. 4. Brugada, P. and J. Brugada, Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol, 1992. 20(6): p. 1391-6. 5. Antzelevitch, C., Cardiac repolarization. The long and short of it. Europace, 2005. 7 Suppl 2: p. 3-9. 6. Blangy, H., et al., [Prevalence of Brugada syndrome among 35,309 inhabitants of Lorraine screened at a preventive medicine centre]. Arch Mal Coeur Vaiss, 2005. 98(3): p. 175-80. 7. Bozkurt, A., et al., Frequency of Brugada-type ECG pattern (Brugada sign) in Southern Turkey. Int Heart J, 2006. 47(4): p. 541-7. 8. Gervacio-Domingo, G., et al., The Brugada type 1 electrocardiographic pattern is common among Filipinos. J Clin Epidemiol, 2008. 61(10): p. 1067-72. 9. Ito, H., et al., The prevalence and prognosis of a Brugada-type electrocardiogram in a population of middle-aged Japanese-American men with follow-up of three decades. Am J Med Sci, 2006. 331(1): p. 25-9. 10. Nademanee, K., Sudden unexplained death syndrome in Southeast Asia. Am J Cardiol, 1997. 79(6A): p. 10-1. 11. Goh, K.T., T.C. Chao, and C.H. Chew, Sudden nocturnal deaths among Thai construction workers in Singapore. Lancet, 1990. 335(8698): p. 1154. 12. Martini, B., et al., Ventricular fibrillation without apparent heart disease: description of six cases. American heart journal, 1989. 118(6): p. 1203-9. 13. Brugada, J., R. Brugada, and P. Brugada, Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation, 2003. 108(25): p. 3092-6. 14. Brugada, P. and J. Brugada, Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. Journal of the American College of Cardiology, 1992. 20(6): p. 1391-6. 15. Wilde, A.A., et al., Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J, 2002. 23(21): p. 1648-54. 16. Brugada, J., R. Brugada, and P. Brugada, Right bundle-branch block and ST-segment elevation in leads V1 through V3: a marker for sudden death in patients without demonstrable structural heart disease. Circulation, 1998. 97(5): p. 457-60. 17. Chen, Q., et al., Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature, 1998. 392(6673): p. 293-6. 18. Alings, M. and A. Wilde, 'Brugada' syndrome: clinical data and suggested pathophysiological mechanism. Circulation, 1999. 99(5): p. 666-73. 19. Wang, Q., et al., SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell, 1995. 80(5): p. 805-11. 20. Hsueh, C.H., et al., Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations. J Biomed Sci, 2009. 16: p. 23. 21. Baroudi, G., et al., Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome. Circ Res, 2002. 90(1): p. E11-6. 22. Mohler, P.J., et al., Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A, 2004. 101(50): p. 17533-8. 23. Grant, A.O., Electrophysiological basis and genetics of Brugada syndrome. J Cardiovasc Electrophysiol, 2005. 16 Suppl 1: p. S3-7. 24. Bezzina, C.R., et al., Common sodium channel promoter haplotype in asian subjects underlies variability in cardiac conduction. Circulation, 2006. 113(3): p. 338-44. 25. Rossenbacker, T. and S.G. Priori, The Brugada syndrome. Curr Opin Cardiol, 2007. 22(3): p. 163-70. 26. Watanabe, H., et al., Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest, 2008. 118(6): p. 2260-8. 27. Antzelevitch, C., et al., Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation, 2007. 115(4): p. 442-9. 28. London, B., et al., Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation, 2007. 116(20): p. 2260-8. 29. Ohno, S., et al., KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation. Circ Arrhythm Electrophysiol, 2011. 4(3): p. 352-61. 30. Wang, T.J., et al., Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med, 2006. 355(25): p. 2631-9. 31. Wang, T.J., et al., Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med, 2004. 350(7): p. 655-63. 32. Loukopoulos, P., et al., Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: identification of genetic indicators that predict patient outcome. Cancer Sci, 2007. 98(3): p. 392-400. 33. Alkan, C., B.P. Coe, and E.E. Eichler, Genome structural variation discovery and genotyping. Nat Rev Genet, 2011. 12(5): p. 363-76. 34. Iafrate, A.J., et al., Detection of large-scale variation in the human genome. Nat Genet, 2004. 36(9): p. 949-51. 35. Redon, R., et al., Global variation in copy number in the human genome. Nature, 2006. 444(7118): p. 444-54. 36. Tuzun, E., et al., Fine-scale structural variation of the human genome. Nat Genet, 2005. 37(7): p. 727-32. 37. Kidd, J.M., et al., Mapping and sequencing of structural variation from eight human genomes. Nature, 2008. 453(7191): p. 56-64. 38. Conrad, D.F., et al., Origins and functional impact of copy number variation in the human genome. Nature, 2010. 464(7289): p. 704-12. 39. Sebat, J., et al., Large-scale copy number polymorphism in the human genome. Science, 2004. 305(5683): p. 525-8. 40. Feuk, L., A.R. Carson, and S.W. Scherer, Structural variation in the human genome. Nat Rev Genet, 2006. 7(2): p. 85-97. 41. Freeman, J.L., et al., Copy number variation: new insights in genome diversity. Genome Res, 2006. 16(8): p. 949-61. 42. Bridges, C.B., The Bar 'Gene' a Duplication. Science, 1936. 83(2148): p. 210-1. 43. Fellermann, K., et al., A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet, 2006. 79(3): p. 439-48. 44. Aitman, T.J., et al., Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature, 2006. 439(7078): p. 851-5. 45. Jongmans, M.C., et al., CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet, 2006. 43(4): p. 306-14. 46. Singleton, A.B., et al., alpha-Synuclein locus triplication causes Parkinson's disease. Science, 2003. 302(5646): p. 841. 47. Rovelet-Lecrux, A., et al., APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet, 2006. 38(1): p. 24-6. 48. Pollex, R.L. and R.A. Hegele, Copy number variation in the human genome and its implications for cardiovascular disease. Circulation, 2007. 115(24): p. 3130-8. 49. Barc, J., et al., Screening for copy number variation in genes associated with the long QT syndrome: clinical relevance. J Am Coll Cardiol, 2011. 57(1): p. 40-7. 50. Byrne, J.L., et al., del(20p) with manifestations of arteriohepatic dysplasia. Am J Med Genet, 1986. 24(4): p. 673-8. 51. Greenberg, F., et al., Cytogenetic findings in a prospective series of patients with DiGeorge anomaly. Am J Hum Genet, 1988. 43(5): p. 605-11. 52. Huang, T., et al., Cardiac phenotypes in chromosome 4q- syndrome with and without a deletion of the dHAND gene. Genet Med, 2002. 4(6): p. 464-7. 53. Pauli, R.M., et al., Ventricular noncompaction and distal chromosome 5q deletion. Am J Med Genet, 1999. 85(4): p. 419-23. 54. Matsuoka, R., et al., Congenital heart anomalies in the trisomy 18 syndrome, with reference to congenital polyvalvular disease. Am J Med Genet, 1983. 14(4): p. 657-68. 55. Van Praagh, S., et al., Cardiac malformations in trisomy-18: a study of 41 postmortem cases. J Am Coll Cardiol, 1989. 13(7): p. 1586-97. 56. Gantt, P.A., et al., A clinical and cytogenetic study of fifteen patients with 45,X/46XY gonadal dysgenesis. Fertil Steril, 1980. 34(3): p. 216-21. 57. Locke, D.P., et al., BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. J Med Genet, 2004. 41(3): p. 175-82. 58. Itsara, A., et al., Population analysis of large copy number variants and hotspots of human genetic disease. Am J Hum Genet, 2009. 84(2): p. 148-61. 59. Snijders, A.M., et al., Assembly of microarrays for genome-wide measurement of DNA copy number. Nat Genet, 2001. 29(3): p. 263-4. 60. Pinkel, D., et al., High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet, 1998. 20(2): p. 207-11. 61. Wang, D.G., et al., Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science, 1998. 280(5366): p. 1077-82. 62. McCarroll, S.A., et al., Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat Genet, 2008. 40(10): p. 1166-74. 63. Cooper, G.M., et al., Systematic assessment of copy number variant detection via genome-wide SNP genotyping. Nat Genet, 2008. 40(10): p. 1199-203. 64. Peiffer, D.A., et al., High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping. Genome Res, 2006. 16(9): p. 1136-48. 65. Winchester, L., C. Yau, and J. Ragoussis, Comparing CNV detection methods for SNP arrays. Brief Funct Genomic Proteomic, 2009. 8(5): p. 353-66. 66. Wei, Q., et al., Testing computational prediction of missense mutation phenotypes: functional characterization of 204 mutations of human cystathionine beta synthase. Proteins, 2010. 78(9): p. 2058-74. 67. Teng, S., E. Michonova-Alexova, and E. Alexov, Approaches and resources for prediction of the effects of non-synonymous single nucleotide polymorphism on protein function and interactions. Curr Pharm Biotechnol, 2008. 9(2): p. 123-33. 68. Wilde, A.A., et al., Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation, 2002. 106(19): p. 2514-9. 69. Antzelevitch, C., et al., Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation, 2005. 111(5): p. 659-70. 70. Antzelevitch, C., et al., Brugada syndrome: report of the second consensus conference. Heart Rhythm, 2005. 2(4): p. 429-40. 71. Ishigami, T., et al., Genes and molecular pathways related to radioresistance of oral squamous cell carcinoma cells. Int J Cancer, 2007. 120(10): p. 2262-70. 72. Saban, M.R., et al., Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG), LPS, and TNF-alpha. BMC Immunol, 2008. 9: p. 4. 73. Yan, B., et al., Systems biology-defined NF-kappaB regulons, interacting signal pathways and networks are implicated in the malignant phenotype of head and neck cancer cell lines differing in p53 status. Genome Biol, 2008. 9(3): p. R53. 74. Bliek, B.J., et al., Genome-wide pathway analysis of folate-responsive genes to unravel the pathogenesis of orofacial clefting in man. Birth Defects Res A Clin Mol Teratol, 2008. 82(9): p. 627-35. 75. Wognum, S., et al., An exploratory pathways analysis of temporal changes induced by spinal cord injury in the rat bladder wall: insights on remodeling and inflammation. PLoS One, 2009. 4(6): p. e5852. 76. Thewes, V., et al., Interference with activator protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells. BMC Cancer, 2010. 10: p. 192. 77. Barr, T.L., et al., Genomic biomarkers and cellular pathways of ischemic stroke by RNA gene expression profiling. Neurology, 2010. 75(11): p. 1009-14. 78. Baer, M., et al., Structure and transcription of a human gene for H1 RNA, the RNA component of human RNase P. Nucleic Acids Res, 1990. 18(1): p. 97-103. 79. Kolacsek, O., et al., Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers. Mob DNA, 2011. 2(1): p. 5. 80. Komura, D., et al., Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays. Genome Res, 2006. 16(12): p. 1575-84. 81. Udomsinprasert, R., et al., Identification, characterization and structure of a new Delta class glutathione transferase isoenzyme. Biochem J, 2005. 388(Pt 3): p. 763-71. 82. Sheehan, D., et al., Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J, 2001. 360(Pt 1): p. 1-16. 83. Jourenkova-Mironova, N., et al., Glutathione S-transferase GSTM3 and GSTP1 genotypes and larynx cancer risk. Cancer Epidemiol Biomarkers Prev, 1999. 8(2): p. 185-8. 84. Welfare, M., et al., Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer. Cancer Epidemiol Biomarkers Prev, 1999. 8(4 Pt 1): p. 289-92. 85. Yengi, L., et al., Polymorphism at the glutathione S-transferase locus GSTM3: interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma. Cancer Res, 1996. 56(9): p. 1974-7. 86. Jourenkova-Mironova, N., et al., Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of smoking-related oral and pharyngeal cancers. Int J Cancer, 1999. 81(1): p. 44-8. 87. Jourenkova-Mironova, N., et al., High-activity microsomal epoxide hydrolase genotypes and the risk of oral, pharynx, and larynx cancers. Cancer Res, 2000. 60(3): p. 534-6. 88. To-Figueras, J., et al., Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population. Environ Health Perspect, 2000. 108(7): p. 595-8. 89. Park, L.Y., et al., Comparison of GSTM polymorphisms and risk for oral cancer between African-Americans and Caucasians. Pharmacogenetics, 2000. 10(2): p. 123-31. 90. Catterall, W.A., From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron, 2000. 26(1): p. 13-25. 91. Lee, J.H., L.L. Cribbs, and E. Perez-Reyes, Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels. FEBS Lett, 1999. 445(2-3): p. 231-6. 92. Bezanilla, F., The voltage sensor in voltage-dependent ion channels. Physiol Rev, 2000. 80(2): p. 555-92. 93. Clapham, D.E., TRP channels as cellular sensors. Nature, 2003. 426(6966): p. 517-24. 94. Lu, B., et al., The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm. Cell, 2007. 129(2): p. 371-83. 95. Lu, T.Z. and Z.P. Feng, A sodium leak current regulates pacemaker activity of adult central pattern generator neurons in Lymnaea stagnalis. PLoS One, 2011. 6(4): p. e18745. 96. Wang, K.S., X.F. Liu, and N. Aragam, A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophr Res, 2010. 124(1-3): p. 192-9. 97. Swayne, L.A., et al., The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic beta-cell line. EMBO Rep, 2009. 10(8): p. 873-80. 98. Swayne, L.A., et al., The NALCN ion channel is a new actor in pancreatic beta-cell physiology. Islets, 2010. 2(1): p. 54-6. 99. Job, B., et al., Genomic aberrations in lung adenocarcinoma in never smokers. PLoS One, 2010. 5(12): p. e15145. 100. Kang, J.U., et al., Gain at chromosomal region 5p15.33, containing TERT, is the most frequent genetic event in early stages of non-small cell lung cancer. Cancer Genet Cytogenet, 2008. 182(1): p. 1-11. 101. Antzelevitch, C., The Brugada syndrome: diagnostic criteria and cellular mechanisms. Eur Heart J, 2001. 22(5): p. 356-63. 102. Thygesen, K., J.S. Alpert, and H.D. White, Universal definition of myocardial infarction. Eur Heart J, 2007. 28(20): p. 2525-38. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66197 | - |
dc.description.abstract | Brugada症候群(Brugada Syndrome, BrS)是一種心臟疾病且會因致死性的心律不整而造成高危險性的突發性死亡,尤其常好發於亞洲輕壯年男性。在先前的研究已顯示,SCN5A突變會造成病患有Brugada症候群的心電圖,但僅有20-25%的Brugada症候群病患有SCN5A突變。然而,對於Brugada症候群的基因體變異(genomic variant),仍尚未被廣泛的研究。因此,本篇論文主是萃取出未帶有SCN5A突變之Brugada症候群病患(n=16)與健康控制組(n=16)的血液中DNA,並且利用全基因性之單一核苷酸多型性 (single-nucleotide polymorphism, SNP)微陣列晶片分析出基因型變異。此群Brugada症候群病患與健康控制組的基因型(genotyping)被分析出來後,本論文利用以下標準並且使用Partekâ軟體分析出拷貝數目變異 (copy number variation, CNV)區段:(1) 樣品基因型的強度 (intensity)標準化後,晶片上每單一核甘酸多型性之拷貝數目(copy number, CN)須至少大於2.3或是小於1.7。(2)每樣品的拷貝數目變異區段需由至少大於100個連續之單一核甘酸多型性位點變異所組成。(3)相鄰拷貝數目變異區段的P-value檢定至少小於10-4。(4)至少有37.5%的樣品在同個拷貝數目變異區域有變異。本篇研究顯示出其中有502個拷貝數目變異區域,這些區域中包含447個區域為拷貝數目減少及55個區域為拷貝數目增加。再者,將這些拷貝數目變異區域與資料庫比對後,結果顯示出有138個基因 (genes)於其中,並且將這些基因利用Ingenuity Pathways Analysis (IPA) 分析出它們的功能。其中最顯著的訊息傳導路徑裡,GSTM3是具有最低的拷貝數目。另外,因Brugada症候群被猜測與離子通道失去功能有相關,故本篇論文找到NALCN是離子通道中有最低拷貝數目。而後,本篇研究藉由多重聚合酶連鎖反應(multiplex PCR)之實驗驗證出Brugada症候群病患有GSTM3和NALCN的拷貝數目減少之現象。此外,本篇論文增加樣品數目並且顯示評估靈敏度(sensitivity)和特異度(specificity) 預測表現後,實驗結果顯示GSTM3和NALCN可成為生物標記(biomarkers)做為診斷Brugada症候群。除此之外,將GSTM3和NALCN交集起來做準確度(accuracy)預測結果後,本研究顯示GSTM3和NALCN具有加成作用。 | zh_TW |
dc.description.abstract | Brugada syndrome (BrS) is a cardiac disease, which results in a high risk of sudden death by lethal arrhythmia, especially in Asian young males. Previous studies reported that it is associated with SCN5A mutations. However, these mutations can only account for 20-25% of BrS patients. The genomic aberration of BrS still remains unclear. Therefore, we have conducted a genome-wide screening from blood of BrS patients without SCN5A mutations using Illumina Omni1-Quad single-nucleotide polymorphism (SNP) chips. The genotypes of BrS patients without SCN5A mutations (n=16) and healthy controls (n=16) were examined. Regions of copy number variation (CNV) were identified by Partekâ software. We have used the following criteria: First, copy number ratio of sample intensity to mean intensity for each SNP is >2.3 or <1.7. Secondly, ≥100 continuous SNP variant loci occur in each sample. Thirdly, P-value ≦ 10-4. Finally, ≥37.5% of samples have common aberration regions. We have identified 502 common aberration regions, with 447 loss and 55 gain regions. Moreover, we have found those common aberration regions containing 138 genes and their functions have been further analyzed using Ingenuity Pathways Analysis. Among these, GSTM3 had the lowest copy number compared to other genes in the top one enriched pathway. Since BrS may be caused by the abnormality of ion channel, we have also focused on NALCN, which encodes sodium channel. Next, the absence of GSTM3 and NALCN were examined by using multiplex PCR in BrS patients. This study has showed that GSTM3 and NALCN lost in BrS patients. Also, the study has evaluated the prediction outcomes in two aspects: one is sensitivity and the other is specificity, and the results have demonstrated that GSTM3 and NALCN might be used as diagnostic biomarkers of detecting BrS. Furthermore, the prediction outcomes of the intersection of GSTM3 and NALCN have indicated that GSTM3 and NALCN could be additive. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T00:25:15Z (GMT). No. of bitstreams: 1 ntu-101-R98441004-1.pdf: 1673732 bytes, checksum: c57475d824d859461168f8a95168563e (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 中文摘要………………………………………………..………………………………….....…………….i
Abstract……………………………………………………………………………………...…………....iii Chapter 1 Introduction…………………………………..………………………………………….…….1 1.1 Heart in Human………………………...…………...…………………………….......…………….1 1.2 Brugada Syndrome and its Related Ion Channels……………………......…………………………1 1.3 Biomarker to Screen Disease……………………………...………………………......………........3 1.4 Genome Structural Variation and Copy Number Variation in Cardiovascular Disease in Human………..…………………………………………………………………..…………..……..4 1.5 Methods of Detection of Structural Variation…………………...….………………………………5 1.6 Motivation and Specific Aims………………………...…………………….………………………7 Chapter 2 Materials and Methods…………………………....…………………………….…………….8 2.1 Study Subjects and Controls……………..…………………...………………………………..........8 2.2 Ethics Statement…………………………………...………………………………………………..9 2.3 Sample Preparation……………………………………...…………………………………………..9 2.4 DNA Extraction……………….………………………...…………………………………………..9 2.5 Microarray Experiments………….……………………...………………………………………...10 2.6 Microarrray Data Analysis……………………...…………………………………………………10 2.7 Multiplex PCR……………………………...………………...……………………………………11 2.8 Statistical Analysis……………………………..……………………………...…………………..12 Chapter 3 Results………………………………………………………………………………………...13 3.1 Clinical Characteristics of the Patients with Brugada Syndrome………………..………………...13 3.2 The Overview of Copy Number Variation (CNV) Regions in Brugada Syndrome (BrS) without SCN5A Genetic Variants……..………..…………..…...……….……………………………..…..13 3.3 The Enriched Pathways of 138 Genes with Aberration Regions in BrS Patients.......…….………14 3.4 Validation of the Copy Number Loss of GSTM3 in BrS Patient……………………...…………..15 3.5 Validation of the Copy Number Loss of NALCN in BrS Patients…………….……...……………15 3.6 GSTM3 and NALCN could be Diagnostic Biomarkers of Predicting BrS….………...…………...16 Chapter 4 Discussion………………………………………….…………………………...…………….18 4.1 Selection of the Proportion of Total Aberration Samples……………………………...………….18 4.2 Validation of the Result from Microarray Using Multiplex PCR…………….…………...…..…..19 4.3 The Approaches to Prove the Mechanism of GSTM3 and NALCN in BrS….........…………….…20 4.4 RPPH1 is a Negative Control and Reference in BrS Patients………………........….………..…...22 4.5 The Genome-wide Map was Different from AMI, BrS, and AF….………….......……...………..22 4.6 Summary…………………………………………………...…...…...…………...………………..24 4.7 Future Work…………….……………………...………………………………...………………..24 Chapter 5 References………………………………………………………………….….……..….……25 Chapter 6 Figures…………….……………………………………………...…………………………..36 Chapter 7 Tables…………………………………………………………………………………………47 | |
dc.language.iso | en | |
dc.title | 藉由拷貝數目變異來分析可能成為具診斷性的Brugada症候群之生物標記 | zh_TW |
dc.title | The Potential Diagnostic Biomarkers of Brugada Syndrome Identified by Copy Number Variation Analysis | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 莊曜宇,江福田 | |
dc.subject.keyword | Brugada症候群,拷貝數目變異,GSTM3,NALCN,多重聚合酶,連鎖反應,生物標記, | zh_TW |
dc.subject.keyword | Brugada syndrome,copy number variants,GSTM3,NALCN,multiplex PCR,biomarkers, | en |
dc.relation.page | 50 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-03-30 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-101-1.pdf 目前未授權公開取用 | 1.63 MB | 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。