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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 李建南 | |
dc.contributor.author | Pei-Wen Kuo | en |
dc.contributor.author | 郭佩雯 | zh_TW |
dc.date.accessioned | 2021-06-08T04:26:11Z | - |
dc.date.copyright | 2011-10-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-17 | |
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Beggs AH, Koenig M, Boyce FM, Kunkel LM. Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 1990;86(1):45-8. 14. Emery AE. The muscular dystrophies. Lancet 2002;359(9307):687-95. 15. Ervasti JM, Sonnemann KJ. Biology of the striated muscle dystrophin-glycoprotein complex. Int Rev Cytol 2008;265:191-225. 16. Blake DJ, Weir A, Newey SE, Davies KE. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 2002;82(2):291-329. 17. Sadoulet-Puccio HM, Kunkel LM. Dystrophin and its isoforms. Brain Pathol 1996;6(1):25-35. 18. Winder SJ. The membrane-cytoskeleton interface: the role of dystrophin and utrophin. J Muscle Res Cell Motil 1997;18(6):617-29. 19. Saiki RK, Scharf S, Faloona F, et al. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985;230(4732):1350-4. 20. Saiki RK, Gelfand DH, Stoffel S, et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239(4839):487-91. 21. Kryndushkin DS, Alexandrov IM, Ter-Avanesyan MD, Kushnirov VV. Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104. J Biol Chem 2003;278(49):49636-43. 22. Schwartz M, Duno M. Improved molecular diagnosis of dystrophin gene mutations using the multiplex ligation-dependent probe amplification method. Genet Test 2004;8(4):361-7. 23. Hung CC, Chen CP, Lin SP, et al. Quantitative assay of deletion or duplication genotype by capillary electrophoresis system: Application in Prader-Willi syndrome and Duchenne muscular dystrophy. Clin Chem 2006;52(12):2203-10. 24. Janssen B, Hartmann C, Scholz V, Jauch A, Zschocke J. MLPA analysis for the detection of deletions, duplications and complex rearrangements in the dystrophin gene: potential and pitfalls. Neurogenetics 2005;6(1):29-35. 25. Todorova A, Todorov T, Georgieva B, et al. MLPA analysis/complete sequencing of the DMD gene in a group of Bulgarian Duchenne/Becker muscular dystrophy patients. Neuromuscul Disord 2008;18(8):667-70. 26. Gatta V, Scarciolla O, Gaspari AR, et al. Identification of deletions and duplications of the DMD gene in affected males and carrier females by multiple ligation probe amplification (MLPA). Hum Genet 2005;117(1):92-8. 27. Liew M, Pryor R, Palais R, et al. Genotyping of single-nucleotide polymorphisms by high-resolution melting of small amplicons. Clin Chem 2004;50(7):1156-64. 28. Flanigan KM, Dunn DM, von Niederhausern A, et al. DMD Trp3X nonsense mutation associated with a founder effect in North American families with mild Becker muscular dystrophy. Neuromuscul Disord 2009;19(11):743-8. 29. Flanigan KM, von Niederhausern A, Dunn DM, Alder J, Mendell JR, Weiss RB. Rapid direct sequence analysis of the dystrophin gene. Am J Hum Genet 2003;72(4):931-9. 30. Ferreiro V, Szijan I, Giliberto F. Detection of germline mosaicism in two Duchenne muscular dystrophy families using polymorphic dinucleotide (CA)n repeat loci within the dystrophin gene. Mol Diagn 2004;8(2):115-21. 31. Den Dunnen JT, Grootscholten PM, Bakker E, et al. Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. Am J Hum Genet 1989;45(6):835-47. 32. Hoffman EP, Brown RH, Jr., Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987;51(6):919-28. 33. Hung CC, Su YN, Lin CY, et al. Denaturing HPLC coupled with multiplex PCR for rapid detection of large deletions in Duchenne muscular dystrophy carriers. Clin Chem 2005;51(7):1252-6. 34. Baumbach LL, Chamberlain JS, Ward PA, Farwell NJ, Caskey CT. Molecular and clinical correlations of deletions leading to Duchenne and Becker muscular dystrophies. Neurology 1989;39(4):465-74. 35. Darras BT, Blattner P, Harper JF, Spiro AJ, Alter S, Francke U. Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: location of breakpoints on HindIII and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations. Am J Hum Genet 1988;43(5):620-9. 36. Gillard EF, Chamberlain JS, Murphy EG, et al. Molecular and phenotypic analysis of patients with deletions within the deletion-rich region of the Duchenne muscular dystrophy (DMD) gene. Am J Hum Genet 1989;45(4):507-20. 37. Lindlof M, Kiuru A, Kaariainen H, et al. Gene deletions in X-linked muscular dystrophy. Am J Hum Genet 1989;44(4):496-503. 38. Takeshima Y, Yagi M, Okizuka Y, et al. Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J Hum Genet 2010;55(6):379-88. 39. Howard MT, Anderson CB, Fass U, et al. Readthrough of dystrophin stop codon mutations induced by aminoglycosides. Ann Neurol 2004;55(3):422-6. 40. Gurvich OL, Maiti B, Weiss RB, Aggarwal G, Howard MT, Flanigan KM. DMD exon 1 truncating point mutations: amelioration of phenotype by alternative translation initiation in exon 6. Hum Mutat 2009;30(4):633-40. 41. Kano Y, Wada M, Imamoto F. Genetic characterization of the gene hupA encoding the HU-2 protein of Escherichia coli. Gene 1988;69(2):331-5. 42. Koenig M, Beggs AH, Moyer M, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 1989;45(4):498-506. 43. Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 1988;2(1):90-5. 44. Plumridge G, Metcalfe A, Coad J, Gill P. Family communication about genetic risk information: particular issues for Duchenne muscular dystrophy. Am J Med Genet A 2010;152A(5):1225-32. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22732 | - |
dc.description.abstract | 裘馨氏肌肉萎縮症(Duchenne muscular dystrophy)和貝克氏肌肉萎縮症(Becker muscular dystrophy),是一種性聯隱性遺傳病,也是兒童期最常見的肌肉萎縮症。致病原因是由於dystrophin基因突變導致肌肉細胞不能正常產生肌縮蛋白,會使鈣離子滲入細胞,使肌纖維壞死,進而導致患者全身肌肉無力。
結合臨床診斷和基因檢測以利裘馨氏肌肉萎縮症或貝克氏肌肉萎縮症準確且有效率診斷流程。建立台灣裘馨氏肌肉萎縮症和貝克氏肌肉萎縮症之資料庫,了解台灣地區是否有特定突變區域,已利提供未來治療的方針。因dystrophin基因非常龐大,單點突變的偵測非常費時,以高分辨熔解分析技術(High-Resolution Melting, HRM)針對dystrophin基因進行分析,可以減短基因檢測分析時間並提供準確基因分析結果。 有288家庭總共551個案利用Multiplex Ligation-dependent Probe Amplification , MLPA和multiplex PCR進行血液基因檢測,結果為突變模式是大片段外顯子的缺失有99的家庭數,大片段外顯子的重覆有39的家庭數。利用以高分辨熔解分析技術(High-Resolution Melting;HRM)和Single-condition amplification/internal primer (SCAIP )進行基因檢測,有72的家庭數是小片段缺失或重複和點突變。 因此,結合臨床診斷和全方位的基因檢測流程能提高裘馨氏肌肉萎縮症或貝克氏肌肉萎縮症的診斷率;根據目前結果能初步建立台灣之裘馨氏肌肉萎縮症或貝克氏肌肉萎縮症的資料庫,希望進而能運用於未來治療或幫助裘馨氏肌肉萎縮症與貝克氏肌肉萎縮症的家庭進行遺傳諮詢。 | zh_TW |
dc.description.abstract | Duchenne muscular dystrophy, DMD and Becker muscular dystrophy, BMD are severe recessive X-link muscular dystrophies that commonly occur during childhood. The disorder is caused by a mutation of the dystrophin gene (DMD gene) which encoded the dystrophin. Absence of dystrophin leads to excess calcium to penetrate the sarcolemma, which is called the cascading process, and results in muscle weakness overall.
In order to provide a more accurate and efficient procedure of diagnosis, we shall combine clinical diagnosis with genetic examination. By establishing the DMD and BMD database among Taiwanese, we can identify the hotspots mutation, and thus provide potential treatments. The detection of point mutations is quite time-consuming because of the huge size of DMD gene. By the application of High Resolution Melting (HRM) analysis, we can reduce the time for examination and also provide accurate results. With Multiplex Ligation-dependent Probe Amplification (MLPA) and multiplex PCR, we examined 288 families, 551 individual, for level I genetic analysis. Deletions of one or more exons account for 99 of families, and duplication of one or more exons account for 39 of families. Furthermore, we apply HRM analysis and Single-condition amplification/internal primer (SCAIP) to examine the level II genetic analysis, and observed 72 families with exonic small deletion, duplication and point mutation. The diagnostic yield of DMD and BMD can be improved with cooperating comprehensive genetic approaches and clinical symptom/signs. We have established the genetic database of DMD/BMD in Taiwan, which may help the therapeutic potential and genetic counseling in the families with DMD/BMD. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:26:11Z (GMT). No. of bitstreams: 1 ntu-100-P98448005-1.pdf: 4889031 bytes, checksum: 7af0b170700afcce65740fbabdf234b0 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 目錄
目次 口試委員會審定書.....................................................................................................Ⅰ 致謝.............................................................................................................................Ⅱ 中文摘要.....................................................................................................................Ⅲ 英文摘要.....................................................................................................................Ⅴ 目錄.............................................................................................................................Ⅶ 第一章 緒論................................................................................................................1 1.1研究動機..................................................................................................1 1.2疾病簡介: ................................................................................................1 1.3遺傳模式..................................................................................................2 1.4臨床症狀..................................................................................................2 1.5疾病病因..................................................................................................3 1.6肌縮蛋白(dystrophin)結構.......................................................................4 第二章 研究方法.........................................................................................................5 2.1實驗材料...................................................................................................5 2.1.1檢體來源............................................................................................5 2.1.2DNA萃取...........................................................................................5 2.1.3引子對................................................................................................5 2.1.4聚合酶連鎖反應試劑........................................................................5 2.1.5 DHPLC試劑組..................................................................................5 2.1.6洋菜膠電泳試劑.................................................................................6 2.1.7 MLPA試劑組....................................................................................6 2.1.8 HRM試劑組......................................................................................6 2.1.9 DNA定序試劑..................................................................................6 2.2實驗儀器.....................................................................................................7 2.3實驗方法.....................................................................................................7 2.3.1DNA萃取...........................................................................................7 2.3.2聚合酶連鎖反應(Polymerase Chain Reaction)............................7 2.3.3洋菜膠電泳(Agarose gel electrophoresis)....................................8 2.3.4Multiplex Polymerase Chain Reaction................................................8 2.3.5Multiplex Ligation-dependent ProbeAmplification.............................8 2.3.6高解析基因突變篩檢分析(High-Resolution Meltin)........................8 2.3.7Single-condition amplification/internal primer (SCAIP) ....................9 第三章 結果..............................................................................................................10 3.1基因突變的分佈........................................................................................10 3.2基因突變的熱區......... ..............................................................................10 3.3基因點突變型分布....................................................................................11 3.4框構轉移突變(frame-shifting mutation) ..................................................11 3.5臨床生化數值和肌肉病理組織切片結果................................................11 3.6 High Resolution Melting(HRM)分析........................................................12 第四章 討論..............................................................................................................13 4.1基因檢測和臨床症狀相關性....................................................................13 4.2基因檢測方法............................................................................................14 4.3基因檢測的系統的流程.............................................................................14 4.4基因突變形式討論....................................................................................15 4.5框構轉移突變(frame-shifting mutation) ..................................................17 4.6遺傳諮詢重要性........................................................................................18 第五章 結論..............................................................................................................19 第六章 致謝..............................................................................................................20 參考文獻..................... ................................................................................................21 圖目錄 目次 Fig 1框構轉移突變(frame-shifting mutation) .....................................................24 Fig 2 Dystrophin . ..................................................................................................25 Fig 3 Dystrophin-Glycoprotein Complex...............................................................26 Fig 4 Multiplex Polymerase Chain Reaction..........................................................27 Fig 5 Multiplex Ligation-dependent Probe Amplification......................................28 Fig 6全部家庭數檢測分佈...................................................................................29 Fig 7 genetic analysis negative familys..................................................................30 Fig 8基因檢測檢測率(1).......................................................................................31 Fig 9基因檢測檢測率(2).......................................................................................32 Fig 10 DMD gene外顯子大片段缺失分佈區.......................................................33 Fig 11 DMD gene外顯子大片段重複分佈區.......................................................34 Fig 12 DMD gene 點突變分區..............................................................................35 Fig13點突變型式分(1) ..........................................................................................36 Fig 14點突變型式分(2) .........................................................................................37 Fig 15BMD/IMD/DMD個案frame-shifting mutation...........................................38 Fig 16 BMD/IMD/DMD個案CPK平均值...........................................................39 Fig 17 High Resolution Melting(HRM)法...............................................................40 Fig 18 BMD/IMD/DMD個案發病紀.....................................................................41 Fig 19 MULTIPLEX PCR 和MLPA 較................................................................42 Fig 20 SEQUENCE 和HRM 之較........................................................................43 Fig 21基因檢測流圖...............................................................................................44 表目錄 目次 Table 1 SEQUENCE 引子總表...............................................................................45 Table 2 HRM 引子對總表.......................................................................................51 Table 3大片段缺失個案總表..................................................................................57 Table 4點突變個案總表..........................................................................................62 Table 5大片段複製個案總表..................................................................................66 | |
dc.language.iso | zh-TW | |
dc.title | 建立裘馨氏肌肉萎縮症和貝克氏肌肉萎縮症之全方位基因分析策略 | zh_TW |
dc.title | Comprehensive Genetic Analysis in Duchenne/Becker Muscular Dystrophy | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 蘇怡寧 | |
dc.contributor.oralexamcommittee | 鐘育志 | |
dc.subject.keyword | 裘馨氏肌肉萎縮症,貝克氏肌肉萎縮症,高解析基因突變篩檢分析,外顯子, | zh_TW |
dc.subject.keyword | Duchenne muscular dystrophy,Becker muscular dystrophy,High Resolution Melting,Exon, | en |
dc.relation.page | 67 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-08-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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