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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李銘仁(Ming-Jen Lee) | |
| dc.contributor.author | Chin-Wen Yang | en |
| dc.contributor.author | 楊錦雯 | zh_TW |
| dc.date.accessioned | 2021-06-08T07:22:29Z | - |
| dc.date.copyright | 2008-08-08 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-24 | |
| dc.identifier.citation | AI-Fifi S, Teebi AS, Shevell M. Autosomal dominant Russell-Silver syndrome. Am J Med Genet 1996; 61: 96-97.
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Genomic imprinting and epigenetic reprogramming: Unearthing the garden of forking paths. Mol Reprod Dev 2002; 63: 269-272. Koufos A, Grundy P, Morgan K, Aleck KA, Lampkin BC, Kalbakji A, Cavenee WK. Familia Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. Am J Hum Genet 1989; 44: 711-719. Koontz WL, Shaw LA, RN, Lavery JP. Antenatal Sonographic Appearance of Beckwith-Wiedemann syndrome. J Clin Ultrasound 1986; 14: 57-59. Li M, Squire JA, Weksberg R. Molecular genetics of Wiedemann-Beckwith syndrome. Am J Med Genet 1998; 79: 253-259. Maher ER and Reik W. Beckwith-Wiedemann syndrome: imprinting in clusters revisited. J Clin Invest 2000; 105: 247-252. McCann J A, Zheng H, Islam A, Goodyer CG, Polychronakos C. Evidence against GRB10 as the gene responsible for Silver-Russell syndrome. Biochem Biophys Res Commun 2001; 286: 943-948. Midro AT, Debek K, Sawicka A, Marcinkiewicz D, Rogowska M. Second observation of Silver-Russel syndrome in a carrier of a reciprocal translocation with one breakpoint at site 17q25. Clin Genet 1993; 44: 53-55. Moore GE, Abu-Amero S, Wakeling E, Hitchins M, Monk D, Stanier P, Preece M. The search for the gene for Silver-Russell syndrome. Acta Paediatr Suppl 1999; 88: 42-48. Murrell A, Heeson S, Reik W. Interaction between differentially methylated regions partitions the imprinted genes IGF2 and H19 into parent-specific chromatin loops. Nat Genet 2004; 36: 889-893. Murrell A, Heeson S, Cooper WL, Douglas E, Apostolidou S, Moore GE, Maher ER, Reik W. An association between variants in the IGF2 gene and Beckwith-Wiedemann syndrome: interaction between genotype and epigenotype. Hum Mol Genet 2004; 13: 247-255. Nakano S, Murakami K, Meguro M, Soejima H, Higashimoto K, Urano T, Kugoh H, Mukai T, Ikeguchi M Oshimura M. Expression profile of LIT1/ KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. Cancer Sci 2006; 97: 1147-1154. Nicholls RD. The impact of genomic imprinting for neurobehavioral and developmental disorders. J Clin Invest 2000; 105: 413-418. Niikawa N, Ishikiriyama S, Takahashi S, Inagawa A, Tonoki H, Ohta Y, Hase N, Kamei T, Kajii T. The Widemann-Beckwith syndrome: pedigree studies on five families with evidence for autosomal dominant inheritance with variable expressivity. Am J Med Genet 1986; 24: 41-55. Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw MA, Smith PJ, Reeve AE. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms’ tumour. Nature 1993; 362: 749-751. Ounap K, Reimand T, Magi M L, Bartsch O. Two sisters with Silver-Russell phenotype. Am J Med Genet A 2004; 131: 301-306. Patton MA. Russell-Silver syndrome. J Med Genet 1988; 25: 557-560. Perkins RM, Hoang-Xuan MA. The Russell-Silver Syndrome: a case report and briefreview ofthe literature. Pediatr Dermatol 2002; 19: 546-549. Pettenati MJ, Haines JL, Higgins RR, Wappner RS, Palmer CG, Weaver DD. Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet 1986; 74: 143-154. Ping AJ, Reeve AE, Law DJ, Young MR, Boehnke M, Feinberg AP. Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. Am J Hum Genet 1989; 44: 720-723. Preece MA, Price SM, Davies V, Clough L, Stanier P, Trembath RC, Moore GE. Maternal uniparental disomy 7 in Silver-Russell syndrome. J Med Genet 1997; 34: 6-9. Price SM, Stanhope R, Garrett C, Preece MA, Trembath RC. The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria. J Med Genet 1999; 36: 837-842. Russell A. A syndrome of intra-uterine-dwarfism recongnizable at birth with cranio-facial dysostosis, disproportionate short arms, and other anomalies （5 samples）. Proc R Soc Med 1954; 47: 1040-1044. Schneid H, Vazquez MP, Vacher C, Gourmelen M, Cabrol S, Le Bouc Y. The Beckwith-Wiedemann syndrome phenotype and the risk of cancer. Med Prediatr Oncol 1997; 28: 411-415. Shuman C, Smith AC, Steele L, Ray PN, Clericuzio C, Zackai E, Parisi MA, Meadows AT, Kelly T, Tichauer D, Squire JA, Sadowski P, Weksberg R. Constitutional UPD for chromosome 11p15 in individuals with isolated hemihyperplasia is associated with high tumor risk and occurs following assisted reproductive technologies. Am J Med Genet 2006; 140: 1497-1503. Smilinich NJ, Day CD, Fitzpatrick GV, Caldwell GM, Lossie AC, Cooper PR, Smallwood AC, Joyce JA, Schofield PN, Reik W, Nicholls RD, Weksberg R, Driscoll DJ, Maher ER, Shows TB, Higgins MJ. A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Widemann syndrome. Proc Natl Acad Sci USA 1999; 96: 8064-8069. Sparago A, Cerrato F, Vernucci M, Ferrero GB, Silengo MC, Riccio A. Microdeletions in the humanH19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome.Nat Genet 2004; 36: 958-960. Silver HK, Kiyasu W, George J, Deamer WC. Syndrome of congenital hemihypertrophy, shortness of stature, and elevated urinary gonadotropins. Pediatrics 1953; 12: 368-376. Weksberg R, Shuman C, Smith AC. Beckwith-Wiedemann syndrome. Am J Med Genet C 2005; 137: 12-23. Weksberg R, Smith AC, Squire J, Sadowski P. Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development. Hum Mol Genet 2003; 12: 61-68. William DH, Gauthier DW, Maizel M. Prenatal diagnosis of Beckwith–Wiedemann syndrome, Prenat Diagn 2005; 25: 879–884. Wolffe AP and Matzke MA. Epigenetics: Regulation through repression. Science 1999; 286: 481-486. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nuceic Acid Res 2003; 31: 3406-3415. http://www.bws-support.org.uk/index.html3 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26721 | - |
| dc.description.abstract | 與人類印痕區域11p15.5相關的甲基化異常遺傳疾病包含貝克威思-威德曼症候群 （Beckwith-Wiedemann syndrome）及羅素-西弗症候群（Russell-Silver syndrome）。導致此兩種疾病發生的主要原因，是由於染色體印痕區域11p15.5上的LIT1與H19基因甲基化程度發生異常。本論文的研究主題有二：(1)開發簡單快速之檢測系統用以偵測甲基化程度的變化（主要是利用甲基化敏感性限制酶結合定量聚合酶連鎖反應），並(2)將此一新開發技術，用於貝克威思-威德曼症候群及羅素-西弗症候群患者LIT1與H19基因座上的DNA甲基化程度檢測。在檢測10名貝克威思-威德曼症候群病患、20名羅素-西弗症候群的病患及20名健康個體LIT1基因的甲基化程度結果中，在健康個體所獲得的基因甲基化指數（Methylation Index; MI）平均值±2個標準差為53.9 %± 14.61（正常參考值：39.29 %~68.51 %）；而在10名貝克威思-威德曼症候群患者的基因甲基化指數中，有五位屬於基因低度甲基化，甲基化指數分別為8.42 %、8.47 %、7.35 %、19.04 %及4.48 %，平均值±2個標準差為9.59 ± 11.08，四位的甲基化指數落於正常參考值範圍內，其值分別為55.28 %、51.34 %、55.87 %及57.8 %；而有ㄧ位甲基化程度介於正常值與低度甲基化之間，甲基化指數為36.7 %，推測這可能與遺傳鑲嵌（genetic mosaicism）現象有關。在羅素-西弗症候群患者裡，LIT1甲基化指數均落在正常參考值範圍內，顯示這些病患可能與LIT1基因甲基化異常無關。在檢測H19基因甲基化時，發現在健康個體所測得的甲基化指數不符合預期(其值均呈現明顯低度甲基化，MI<<1)，以軟體分析經聚合酶連鎖反應擴增後的單股DNA序列發現，分子會形成明顯的二級結構，推測這可能會影響引子黏合（annealing）效率，進而致使所偵測的甲基化指數與預期結果不符；因此，學生目前初步所開發的E-Q-PCR暫時還無法應用於H19基因的甲基化程度檢測。然而，本研究所開發的新技術已證實在LIT1基因座上可以快速準確偵測其甲基化程度變化，此外，本方法只須少量DNA即可進行甲基化程度檢測，因此可將其發展應用於產前篩檢上。 | zh_TW |
| dc.description.abstract | The imprinting regions at chromosome11p15.5 are associated with Beckwith-Wiedemann syndrome (BWS) and Russell-Silver syndrome (RSS). The most frequent findings are the defect of methylation on the imprinting loci LIT1 and H19, both located at chromosome11p15.5, in patients with BWS and RSS. Therefore this study is to develop a simplified and high-performance method for assessment of the degrees of DNA methylation. The novel method is designed by coupling the methylation-sensitive endonuclease treatment and the quantitative polymerase chain reaction (called E-Q-PCR). And the method was employed to evaluate the variable of methylation on the imprinting loci LIT1 and H19. A total of 10 BWS patients, 20 RSS patients and 20 healthy individuals were analysed. The methylation index (MI) of the 20 health individuals was estimated to be ranged from 39.29 %~68.51 % (mean ± 2 SD = 53.9% ± 14.61) which was arbitrarily designated as the normal range of the MI. For the ten BWS patients, five reveal LIT1 hypomethylation with the MI values, 8.42 %, 8.47 %, 7.35 %, 19.04 % and 4.48 % (mean ± 2 SD = 9.59 % ± 11.08 ), four show normal LIT1 methylation pattern, MI= 55.28 %, 51.34 %, 55.89 % and 57.8 %, (mean ± 2 SD = 55.08 % ± 5.42), and one has the MI value (MI= 36.7 %) between the normal and hypomethylation ranges, possibly caused by a genetic mosaicism. For the 20 RSS patients, neither hypomethylation nor hypermethylation was identified. I noted unexpected results were obtained when E-Q-PCR was performed on the H19 locus which might be due to the secondary structure of the single strand DNA produced during PCR. Despite this, E-Q-PCR remains to be a practical method for estimating degrees of DNA methylation since it has been successfully applied on the LIT1 locus. This molecular approach deserves more effort to further characterize its sensitivity, specificity, and cost-effective analyses when compared with other molecular diagnostic techniques. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T07:22:29Z (GMT). No. of bitstreams: 1 ntu-97-P95448010-1.pdf: 6858997 bytes, checksum: cc2d1c64596e16cc6cf4b5c87b9b50d4 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………………………………....Ι
英文摘要……………………………………………………………………………….Ⅲ 目錄……………………………………………………………………………………V 圖目錄及表目錄……………………………………………………………………… Ⅵ 附圖及附表目錄…………………………………………………………………….Ⅶ 第一章 緒論……………………………………………………………………….......1 第一節 基因印痕（genetic imprinting）………………………………………......1 第二節 DNA甲基化（methylation）與基因表現…………………………………2 第三節 與基因印痕有關的遺傳疾病………………………………………….......3 第四節 研究緣由及目的……………………………………………………….......3 第二章 材料與方法………………………………………………………………….12 第一節 實驗材料………………………………………………………………….12 第二節 實驗方法………………………………………………………………….12 第三章 結果………………………………………………………………………….24 第一節 南方墨點法（Southern blot）的結果………………………………….24 第二節 校正曲線之建立………………………………………………………...24 第三節 貝克威思-威德曼症候群與羅素-西弗症候群患者在11p15.5區域基因的甲基化表現…………………………………………………………...26 第四章 討論………………………………………………………………………….29 第五章 總結………………………………………………………………………….39 參考文獻……………………………………………………………………………….41 附件…………………………………………………………………………………….68 圖目錄及表目錄 圖 圖一、人類染色體11p15.5區域之印痕基因群及偵測LIT1基因甲基化程度之實驗設計圖示....………………………………………………………………………….…46 圖二、人類染色體11p15.5區域之印痕基因群及偵測H19基因甲基化程度之實驗設計圖示…………………………………………………………………………….…47 圖三、LIT1/pGEM-T easy 圖譜…………………………………………………..…..48 圖四、H19/pGEM-T easy 圖譜………………………………………………………..49 圖五、南方墨點法電泳結果-LIT1基因………………………………………………50 圖六、LIT1/pGEM-T easy質體經限制酶NotI及EcoRI處理後的電泳結果………51 圖七、LIT1基因校正曲線之建立………………………………………………….…52 圖八、E-Q-PCR-H19基因建立校正曲線結果…………………………………….…53 圖九、限制酶結合定量聚合酶連鎖反應-LIT1基因正常甲基化結果…………..….55 圖十、限制酶結合定量聚合酶連鎖反應（E-Q-PCR）-LIT1基因結果統計圖（ㄧ）………………………………………………………………………………..…56 圖十ㄧ、限制酶結合定量聚合酶連鎖反應-LIT1基因低度甲基化結果……………58 圖十二、限制酶結合定量聚合酶連鎖反應-LIT1基因反應結果電泳圖……………59 圖十三、限制酶結合定量聚合酶連鎖反應-H19基因之健康個體結果…………….60 表 表一、本實驗中所使用引子序列………………………………………………..……61 附圖及附表目錄 附圖 附圖一、超音波下所顯示貝克威思-威德曼症候群疾病之巨舌特徵……………….62 附圖二、貝克威思-威德曼症候群疾病之臍膨出特徵……………………………….63 附圖三、H19基因序列經聚合酶連鎖反應擴增後單股DNA所形成的二級結構…64 附圖四、LIT1基因序列經聚合酶連鎖反應擴增後單股DNA所形成的二級結構…66 附表 附表一、貝克威思-威德曼症候群致病原因……………………………….................67 | |
| dc.language.iso | zh-TW | |
| dc.subject | 甲基化敏感性限制酶 | zh_TW |
| dc.subject | 甲基化 | zh_TW |
| dc.subject | 人類印痕區域11p15.5 | zh_TW |
| dc.subject | 羅素-西弗症候群 | zh_TW |
| dc.subject | 貝克威思-威德曼症候群 | zh_TW |
| dc.subject | 連鎖反應 | zh_TW |
| dc.subject | 結合即時定量聚合酶 | zh_TW |
| dc.subject | Beckwith-Wiedemann syndrome | en |
| dc.subject | Russell-Silver syndrome | en |
| dc.subject | methylation-sensitive endonuclease-coupled quantitative polymerase chain reaction (E-Q-PCR) | en |
| dc.subject | methylation | en |
| dc.subject | imprinting | en |
| dc.title | 人類印痕區域11p15.5遺傳疾病之分析 | zh_TW |
| dc.title | Analysis of Human Imprinting gene 11p15.5 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 余家利(Chia-li Yu),陳明(Ming Chen) | |
| dc.subject.keyword | 人類印痕區域11p15.5,甲基化,甲基化敏感性限制酶,結合即時定量聚合酶,連鎖反應,貝克威思-威德曼症候群,羅素-西弗症候群, | zh_TW |
| dc.subject.keyword | imprinting,methylation,methylation-sensitive endonuclease-coupled quantitative polymerase chain reaction (E-Q-PCR),Beckwith-Wiedemann syndrome,Russell-Silver syndrome, | en |
| dc.relation.page | 71 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2008-07-24 | |
| 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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