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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 | 張淑媛(Sui-Yuan Chang) | |
dc.contributor.author | Jian-Ching Tu | en |
dc.contributor.author | 涂建勍 | zh_TW |
dc.date.accessioned | 2021-06-08T04:15:37Z | - |
dc.date.copyright | 2010-09-13 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-08-06 | |
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(2009) New insights to the MLL recombinome of acute leukemias. (Translated from eng) Leukemia 23(8):1490-1499 (in eng). 41. Meyer C, et al. (2006) The MLL recombinome of acute leukemias. (Translated from eng) Leukemia 20(5):777-784 (in eng). 42. Bowman GD, et al. (2000) Crystal structure of the oligomerization domain of NSP4 from rotavirus reveals a core metal-binding site. (Translated from eng) J Mol Biol 304(5):861-871 (in eng). 43. So CW & Cleary ML (2003) Common mechanism for oncogenic activation of MLL by forkhead family proteins. (Translated from eng) Blood 101(2):633-639 (in eng). 44. Gu Y, et al. (1992) The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase. (Translated from eng) Proc Natl Acad Sci U S A 89(21):10464-10468 (in eng). 45. Lee JA, Carvalho CM, & Lupski JR (2007) A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders. (Translated from eng) Cell 131(7):1235-1247 (in eng). 46. Schwartz JL & Jordan R (1997) Selective elimination of human lymphoid cells with unstable chromosome aberrations by p53-dependent apoptosis. (Translated from eng) Carcinogenesis 18(1):201-205 (in eng). 47. Mohrin M, et al. (2010) Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis. (Translated from Eng) Cell Stem Cell (in Eng). 48. Bonnet D (2005) Cancer stem cells: lessons from leukaemia. (Translated from eng) Cell Prolif 38(6):357-361 (in eng). 49. Moshaver B, et al. (2008) Identification of a small subpopulation of candidate leukemia-initiating cells in the side population of patients with acute myeloid leukemia. (Translated from eng) Stem Cells 26(12):3059-3067 (in eng). 50. Pang R, et al. (2010) A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. (Translated from eng) Cell Stem Cell 6(6):603-615 (in eng). 51. Zhang Q, et al. (2010) A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. (Translated from eng) Cancer Lett 289(2):151-160 (in eng). 52. Dunne J, et al. (2010) AML1/ETO proteins control POU4F1/BRN3A expression and function in t(8;21) acute myeloid leukemia. (Translated from eng) Cancer Res 70(10):3985-3995 (in eng). 53. Westendorf JJ, et al. (1998) The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. (Translated from eng) Mol Cell Biol 18(1):322-333 (in eng). 54. Basecke J, et al. (2002) Transcription of AML1/ETO in bone marrow and cord blood of individuals without acute myelogenous leukemia. (Translated from eng) Blood 100(6):2267-2268 (in eng). 55. Yuan Y, et al. (2001) AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. (Translated from eng) Proc Natl Acad Sci U S A 98(18):10398-10403 (in eng). 56. Spencer CC (2006) Human polymorphism around recombination hotspots. (Translated from eng) Biochem Soc Trans 34(Pt 4):535-536 (in eng). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22328 | - |
dc.description.abstract | 人類基因體的變異主要分為單一核苷酸多型性 (SNPs) 位點以及結構變異(Structural Variation) ;後者包含了刪除 (deletion) 、插入 (insertion) 、倒置 (inversion) 、轉位 (translocation) 與重複 (duplication) 。至今已發現約一千萬個SNPs位點變異,來研究人類遺傳以及表型的變化。此外,人類基因體變異數據資料庫 (Database of Genomic Variants, DGV) 將較大片段的結構變異資料建置資料庫,到2010年趨近九萬筆資料,以拷貝數變異佔最多,約99%。目前對結構變異偵測的主要技術為array-CGH,其可偵測拷貝數改變的結構變異,但卻無法偵測平衡結構變異。平衡結構變異包含倒置及轉位。實驗室先前所建立的技術Restriction Enhanced Capturing Of Rearranged DNA (RECORD) 以inverse PCR為基礎,配合限制酵素切除未轉位模板。在目標基因上做結構變異的偵測,配合序列分析,來決定結構變異。先前已利用RECORD技術在人類精蟲細胞中偵測三種基因之轉位,對在新生兒及幼兒型血癌常見的轉位基因MLL,及幼兒型骨癌常見的轉位基因EWSR1,和兒童型淋巴性白血病轉位基因TCF3。許多研究發現MLL染色體轉位斷裂點呈明顯叢聚分佈;此外,根據之前研究,NHEJ-deficient B細胞在進入周邊組織後,抗體再修飾的發生也會造成染色體的重組,觀察到MYC基因與免疫球蛋白的轉位。本論文的主要研究方向為,以人類的周邊血液單核球細胞Peripheral Blood Mononuclear Cells (PBMCs) 作為實驗材料。利用RECORD技術配合特異性引子,偵測MLL基因在正常人的體細胞是否與生殖細胞具有相同染色體重組之現象。為了確認實驗條件,我們發現RECORD技術可偵測到在RS4;11細胞株帶有t(4;11)(q21;q23)的平衡轉位染色體,帶有相互的轉位的第四對及第十一對染色體。之後,利用RECORD分析25位沒有血癌的正常成人所抽出的周邊血液,來檢測正常人體細胞中是否具有不正常的轉位染色體的存在。實驗結果發現,在不同的正常人的PBMCs細胞中,可以偵測到隨機轉位的染色體結構。其轉位的對象隨機散佈在不同染色體的位置上,由序列方向性推測可以分為三種類型之染色體,為雙中心 (dicentric)、無中心 (ancentric)、單中心 (derivative) 的染色體。細胞複製時的檢查點會使非單中心染色體之細胞無法複製,影響體細胞所偵測之染色體轉位以單中心佔最多。接著由前述25位正常人中隨機挑選10位,利用CD3/CD19螢光抗體標定T及B細胞,經由流式細胞儀分選系統將單核細胞分為B、T、non-B/non-T三類細胞後,同樣利用RECORD偵測轉位,觀察轉位的發生是否在不同細胞間存在有差異。由本研究中發現,生殖細胞的染色體重組的機制,可以保留到個體發育後的細胞內。此機制提供演化的推力而保留於個體,但是否某些偶發性的基因相關疾病與此機制具有相關性,則需要更深入的探討。 | zh_TW |
dc.description.abstract | Variations in the human genome consists of single nucleotide polymorphisms (SNPs) sites, and structural variation (SVs); which contains deletion, insertion, inversion, translocation and duplication. Up to date, more than 10 million SNPs have been used to study human genetic and phenotypic changes. In addition, data on human genome variation database (Database of Genomic Variants, DGV) to larger fragments of the structural variation information data has collected 90,000 document information, among which 99% is copy number variation. The current technology array-CGH can detect changes of copy number variation, but not the balanced structural variation, including inversion and translocation. Our laboratory has previously established the technique Restriction Enhanced Capturing Of Rearranged DNA (RECORD) to determine the target genes structure variation and was shown to detect three kinds of gene translocation, the neonatal and infant leukemia common translocation gene MLL, child care type of bone cancer common translocation gene EWSR1, and child-type lymphoblastic Leukemia translocation gene TCF3 in human sperm cells. In this study, we set to determine whether chromosomal rearrangement also occur in human Peripheral Blood Mononuclear Cells (PBMCs) using MLL as target gene. The RS4; 11 cell lines with t(4; 11)(q21; q23) balanced translocation of chromosomes was first used to determine the experimental conditions and sensitivity of the RECORD. Among the PBMCs from 25 healthy individuals, some random translocation chromosome structure was observed. The object of its translocation chromosomes was scattered in different locations, and the orientation suggested by the sequence can be grouped into three types of chromosomes, the two-center (dicentric), no center (acentric), and single-center (derivative) chromosomes. Flow cytometry sorting was next used to determine the cell types, B, T, and non-B/non-T groups, in which translocations occur. Our preliminary results suggest that germ cell chromosomal rearrangement mechanisms can be retained to differential cells. Our study results provide some information about the mechanism of evolution within individual, yet whether it can be related to some sporadic gene-related diseases and the potential mechanisms require further exploration. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:15:37Z (GMT). No. of bitstreams: 1 ntu-99-R97424023-1.pdf: 3405005 bytes, checksum: e19c86dc5253b1e60b740edaeece28f7 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 主目錄 I
圖目錄 III 表目錄 IV 誌謝 V 中文摘要 1 Abstract 3 壹、緒論 5 1.1 突變、演化與疾病 5 1.2 基因體結構變異 5 1.3 結構變異與疾病 6 1.4 偵測基因體的結構變異 7 1.5 RECORD (Restriction Enhanced Capturing of Rearranged DNA) 技術簡介 8 1.6 MLL(myeloid/lymphoid or mixed-lineage leukemia) 9 1.7 研究方向 10 貳、 實驗材料與方法 11 2.1 實驗材料 11 2.1.1 試藥 11 2.1.2 Kit 12 2.1.3 模板(Templates) 12 2.1.4 引子(Primers) 15 2.1.5 儀器 15 2.1.6 溶液之配製 16 2.2 實驗方法 17 2.2.1 周邊血液單核球細胞(PBMCs)分離 18 2.2.2 流式細胞儀分選 18 2.2.3 細胞株及周邊血液單核球細胞基因體DNA(genomic DNA)萃取 18 2.2.4 模版之前處理 19 2.2.5 長片段反向聚合酶連鎖反應 20 2.2.6 選殖 (cloning) 21 2.2.7 菌落聚合酶連鎖反應(colony PCR) 21 2.2.8 質體insert DNA確認 21 2.2.9 定序結果分析 22 參、 實驗結果 22 3.1 RECORD偵測體細胞MLL基因轉位之條件 22 3.2 以RS4;11細胞株作為RECORD技術在MLL基因上的控制組 23 3.3 25位沒有血癌之正常成人分離之PBMCs分析MLL基因轉位 25 3.4 PBMCs流式細胞儀分選 26 3.5 利用RECORD偵測不同細胞型態細胞轉位情形 26 肆、討論 27 4.1 體細胞之染色體轉位與RECORD技術之運用 27 4.2 RS4;11細胞株利用體細胞偵測條件作為RECORD的控制組 28 4.3 25位正常個體之MLL基因轉位 29 4.4 流式儀細胞分選 30 4.5 RECORD偵測不同細胞型態細胞轉位情形 31 伍、結論 32 參考文獻 34 | |
dc.language.iso | zh-TW | |
dc.title | 正常成人周邊血液單核球細胞之染色體重組 | zh_TW |
dc.title | Chromosomal Rearrangements Detected in Peripheral Blood Mononuclear Cells of Normal Adults | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 常蘭陽 | |
dc.contributor.oralexamcommittee | 林文昌,林東燦,胡忠怡 | |
dc.subject.keyword | 正常成人,周邊血液,染色體重組,轉位, | zh_TW |
dc.subject.keyword | normal adult,PBMC,chromosomal rearrangement,translocation, | en |
dc.relation.page | 77 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2010-08-06 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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