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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 胡務亮 | |
| dc.contributor.author | I-Lei Chien | en |
| dc.contributor.author | 錢薏蕾 | zh_TW |
| dc.date.accessioned | 2021-06-15T00:55:07Z | - |
| dc.date.available | 2008-09-11 | |
| dc.date.copyright | 2008-09-11 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-08-05 | |
| dc.identifier.citation | 1. [Issue dedicated to Professor C. Jimenez Daaz on the occasion of his silver anniversary in the Chair of Medical Pathology of the University of Madrid.]. Rev Clin Esp 1953. 50: 1-2
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Med Phys 1991. 18: 928-33 28. Kotzot D, Schmitt S, Bernasconi F, Robinson WP, Lurie IW, et al. Uniparental disomy 7 in Silver-Russell syndrome and primordial growth retardation. Hum Mol Genet 1995. 4: 583-7 29. Maekawa M, Sugano K, Kashiwabara H, Ushiama M, Fujita S, et al. DNA methylation analysis using bisulfite treatment and PCR-single-strand conformation polymorphism in colorectal cancer showing microsatellite instability. Biochem Biophys Res Commun 1999. 262: 671-6 30. Malcolm S, Clayton-Smith J, Nichols M, Robb S, Webb T, et al. Uniparental paternal disomy in Angelman's syndrome. Lancet 1991. 337: 694-7 31. McGrath J, Solter D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 1984. 37: 179-83 32. Monk D, Bentley L, Hitchins M, Myler RA, Clayton-Smith J, et al. Chromosome 7p disruptions in Silver Russell syndrome: delineating an imprinted candidate gene region. Hum Genet 2002. 111: 376-87 33. Moore GE, Abu-Amero S, Wakeling E, Hitchins M, Monk D, et al. The search for the gene for Silver-Russell syndrome. Acta Paediatr Suppl 1999. 88: 42-8 34. Murrell A, Ito Y, Verde G, Huddleston J, Woodfine K, et al. Distinct methylation changes at the IGF2-H19 locus in congenital growth disorders and cancer. PLoS ONE 2008. 3: e1849 35. Netchine I, Rossignol S, Dufourg MN, Azzi S, Rousseau A, et al. 11p15 imprinting center region 1 loss of methylation is a common and specific cause of typical Russell-Silver syndrome: clinical scoring system and epigenetic-phenotypic correlations. J Clin Endocrinol Metab 2007. 92: 3148-54 36. Nicholls RD. Uniparental disomy as the basis for an association of rare disorders. Am J Med Genet 1991. 41: 273-4 37. Nicholls RD, Pai GS, Gottlieb W, Cantu ES. Paternal uniparental disomy of chromosome 15 in a child with Angelman syndrome. Ann Neurol 1992. 32: 512-8 38. Nussbaum RL, McInnes RR, Willard HF, A H. 2007. Principles of Clinical Cytogenetics. In Genetics in Medicine, ed. Nussbaum RL, McInnes RR, Willard HF, H A, pp. 79: Elsevier Inc. 39. Patton MA. Russell-Silver syndrome. J Med Genet 1988. 25: 557-60 40. Percesepe A, Bertucci E, Ferrari P, Lugli L, Ferrari F, et al. Familial Beckwith-Wiedemann syndrome due to CDKN1C mutation manifesting with recurring omphalocele. Prenat Diagn 2008. 28: 447-9 41. 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: 837-42 42. Rizzo V, Traggiai C, Stanhope R. Growth hormone treatment does not alter lower limb asymmetry in children with Russell-Silver syndrome. Horm Res 2001. 56: 114-6 43. Russell A. A syndrome of intra-uterine dwarfism recognizable at birth with cranio-facial dysostosis, disproportionately short arms, and other anomalies (5 examples). Proc R Soc Med 1954. 47: 1040-4 44. Saal HM. 2007. Russell-Silver Syndrome University of Washington, Seattle 45. Sakatani T, Kaneda A, Iacobuzio-Donahue CA, Carter MG, de Boom Witzel S, et al. Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science 2005. 307: 1976-8 46. Sanlaville D, Aubry MC, Dumez Y, Nolen MC, Amiel J, et al. Maternal uniparental heterodisomy of chromosome 14: chromosomal mechanism and clinical follow up. J Med Genet 2000. 37: 525-8 47. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A 2006. 103: 1412-7 48. Silver HK, Kiyasu W, George J, Deamer WC. Syndrome of congenital hemihypertrophy, shortness of stature, and elevated urinary gonadotropins. Pediatrics 1953. 12: 368-76 49. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975. 98: 503-17 50. Szabo A. The impact of exercise deprivation on well-being of habitual exercises. Aust J Sci Med Sport 1995. 27: 68-75 51. Temple IK. Imprinting in human disease with special reference to transient neonatal diabetes and Beckwith-Wiedemann syndrome. Endocr Dev 2007. 12: 113-23 52. Tsukishiro S, Li QY, Tanemura M, Sugiura-Ogasawara M, Suzumori K, Sonta S. Paternal uniparental disomy of chromosome 14 and unique exchange of chromosome 7 in cases of spontaneous abortion. J Hum Genet 2005. 50: 112-7 53. Tycko B, Morison IM. Physiological functions of imprinted genes. J Cell Physiol 2002. 192: 245-58 54. Wojdacz TK, Dobrovic A, Algar EM. Rapid detection of methylation change at H19 in human imprinting disorders using methylation-sensitive high-resolution melting. Hum Mutat 2008. 55. Wollmann HA, Kirchner T, Enders H, Preece MA, Ranke MB. Growth and symptoms in Silver-Russell syndrome: review on the basis of 386 patients. Eur J Pediatr 1995. 154: 958-68 56. 李美慧. 2007. 羅素–西弗氏症與人類印記基因甲基化的關聯性研究. 國立台灣大學, Taipei | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42245 | - |
| dc.description.abstract | 中文摘要
本實驗主要在探討H19/IGF2區域低度甲基化的情形，與羅素–西弗氏症(Russell–Silver syndrome; RSS)患者臨床表徵間的關聯性。 RSS為一種罕見的先天性遺傳疾病，其特徵有出生前子宮內生長遲滯(intrauterine growth retardation; IUGR)、出生後生長遲緩(Lack of postnatal catch-up growth)、倒三角臉(Triangular face)、身體左右不對稱(Asymmetry)及第五根手指彎斜向內(clinodactyly)等主要特徵，並可能伴隨發展遲緩(Developmental delay)、語言障礙(Delayed speech)、餵食困難(Feeding difficulties)、身體出現咖啡牛奶色斑(Café au lait spots)、肌肉張力低(Muscular hypotonial)、低血糖(Hypoglycemia)等次要特徵，臨床特徵歧異性高。 根據目前研究結果發現，RSS的遺傳模式及病因學複雜且多樣化，多數個案為家族中首例。在病因學方面，除了染色體構造及數目異常外，近年來研究顯示可能與部分基因的甲基化程度有關，其中約7~10%的RSS病患為第七對染色體母源單親二體症(matUPD7)、部分患者為7號染色體鑲嵌型不平衡轉位(mUPD7q31-qter)以及可能因第11對染色體上的H19促進子(promoter)發生低度甲基化的情形造成，近年來研究發現約有50%左右的患者在H19/IGF2區域間甲基化程度有偏低的現象。本實驗針對二十八位具有RSS臨床表徵的病患(五項主要特徵中符合其中三項，並伴有一項次要特徵)，在我們所選定的H19與IGF2基因上游促進子的位置進行人類印記基因(imprinting genes)甲基化程度的檢測，發現七名病患在H19促進子區域有低度甲基化的情形(25%)，而H19與IGF2促進子區域甲基化的程度呈弱相關(R=0.539)。就RSS病人而言， H19區域有低甲基化的患者其臨床表徵在相對正常頭圍的情況與一般RSS患者相比有較高的發生機率。我們的研究顯示IGF2-H19區域的低甲基化對於RSS而言是個主要的致病原因。若將診斷標準定義的更嚴格，以同時具有IUGR及出生後生長發育不良做為RSS患者的必要條件時，則我們所選定的患者中有五位會被歸類於似RSS表徵的患者(SRS-like syndrome)，並且在計算RSS患者低度甲基化的比率上會提高(30.4%)，但在相對正常頭圍的分析上與前述結果無異。 在一些相關報導中發現IGF2/H19低度甲基化的情況會發生在RSS及似RSS表徵的患者身上，此發現可能對於將來在研究生長遲緩等相關研究上至觀重要。而此區域低甲基化患者的臨床特色，亦可提供醫師疾病診斷時之參考。 | zh_TW |
| dc.description.abstract | Abstract
Hypomethylation of the IGF2/H19 locus is associated with a severe phenotype in Silver-Russell syndrome. Russell-Silver syndrome (RSS) is a rare congenital disorder.The major characteristic of RSS include intrauterine growth retardation (IUGR) , lack of postnatal catch-up growth, triangular face, body asymmetry and 5th finger clinodactylyand.Affected individuals may also have diverse symptoms such as developmental delay, delayed speech, feeding difficulties, café au lait spots, muscular hypotonial and hypoglycemia.The clinical picture is extremely diverse. Recently finding,the mode of inheritance is variable with sporadic cases also being described.The etiology of RSS is heterogeneous, but recently hypomethylation of the IGH2/H19 locus is known to explain 50% of the cases. We analyzed 28 patients who fitted in three or more of the five criteria for RSS (IUGR, lack of catch-up growth, characteristic face, asymmetry, and 5th finger clinodactyly). We identified H19 hypomethylation in 7 cases (25%). H19 hypomethylation was correlated to the methylation status of the IGF2 control region. Phenotype analysis revealed a high incidence of preservation of head circumference in cases with IGF2/H19 hypomethylation. When we employed a stricter diagnostic criteria that both IUGR and lack of catch-up growth being essential, a portion of the cases were classified into the SRS-like syndrome, but the percentage of IGF2/H19 hypomethylation in SRS became higher. IGF2/H19 hypomethylation occurred in both RSS and RSS-like syndromes in this study. These materials will be crucial in future researches on the growth retardation syndromes. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T00:55:07Z (GMT). No. of bitstreams: 1 ntu-97-P95448008-1.pdf: 836659 bytes, checksum: 367cbc15b68282fc853302d3b94fb361 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 中文摘要 I
ABSTRACT III 第一章 緒論 1 第一節 羅素–西弗氏症(Russell-Silver Syndrome) 1 1. 起源 1 2. 臨床特徵 1 3. 診斷 3 第二節 基因印記 (genomic imprinting)與DNA甲基化(DNA methylation) 4 1. 什麼是基因印記 4 2. DNA甲基化(DNA methylation) 與基因表現 5 第三節 人類與基因印記有關的遺傳疾病 6 第四節 與生長發育有關的印記基因 6 1. H19 7 2. IGF2 7 3. H19/IGF2 相互作用 8 第五節 比較目前甲基化研究的方法 8 1. DNA甲基化分析的前處理 9 2. DNA甲基化的偵測 10 第二章 研究動機及目的 11 第一節 研究動機 11 第二節 研究目的 11 第三章 實驗材料與研究方法 12 第一節 實驗材料 12 1. 實驗對象 12 2. 引子之設計 13 3. 各項實驗所需試劑 13 4. Quantative PCR所需試劑 14 第二節 研究方法 14 1. 血液檢體 Genomic DNA萃取過程 14 2. 以光譜儀分析DNA濃度 15 3. 限制酵素處理Genomic DNA 16 4. 聚合酶連鎖反應(Polymerase chain reaction；PCR) 16 5. 洋菜膠體之配製(Agarose gel preparation) 17 6. 電泳條件 17 7. PCR產物分析 18 8. 利用Kodak Digital Science ID軟體量化PCR產物甲基化比值 18 9. 定量聚合酶連鎖反應(quantitative PCR; qPCR) 18 第三節 統計方法 19 第四章 實驗結果 20 第一節 H19 promoter區域甲基化的程度在RSS病人及對照組身上具差異性 20 第二節 H19 promoter及H19 ICR區域甲基化的程度在RSS病人及對照組身上具差異性 22 第三節 IGF2區域甲基化的程度在RSS的病人及對照組身上具差異性 22 第四節 H19與IGF2的關係在各群組間甲基化的程度成正比 23 第五節 H19甲基化程度不同的RSS患者在表徵上具差異性 24 第五章 討論 25 第六章 參考文獻 28 表目錄 表 一、與人類印記基因有關的遺傳性疾病 1 表 二、比較利用重亞硫酸鈉與限制酵素處理DNA片段的優缺 2 表 三、為本實驗所選定的基因座位置及引子的序列 3 表 四、本實驗研究的28位RSS病患其臨床表徵(一) 4 表 五、本實驗研究的28位RSS病患其臨床表徵(二) 5 表 六、qPCR反應條件及步驟 6 表 七、比較RSS患者在H19甲基化差異程度及與臨床表徵的關聯性(一) 7 表 八、比較RSS患者在H19甲基化差異程度及與臨床表徵的關聯性(二) 8 | |
| dc.language.iso | zh-TW | |
| dc.subject | H19 | zh_TW |
| dc.subject | IGF2 | zh_TW |
| dc.subject | 羅素–西弗氏症 | zh_TW |
| dc.subject | 甲基化 | zh_TW |
| dc.subject | 印記基因 | zh_TW |
| dc.subject | H19 | en |
| dc.subject | Russell-Silver syndrome | en |
| dc.subject | Methylation | en |
| dc.subject | Imprinting gene | en |
| dc.subject | IGF2 | en |
| dc.title | 羅素–西弗氏症與人類印記基因甲基化的定量與探討 | zh_TW |
| dc.title | The Quantification and Analysis of Methylation of Human Imprinting Genes in Russell-Silver Syndrome | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 余家利,簡穎秀 | |
| dc.subject.keyword | 羅素–西弗氏症,甲基化,印記基因,H19,IGF2, | zh_TW |
| dc.subject.keyword | Russell-Silver syndrome,Methylation,Imprinting gene,H19,IGF2, | en |
| dc.relation.page | 55 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-08-05 | |
| 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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