請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46144完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇怡寧 | |
| dc.contributor.author | Hui-Ping Chou | en |
| dc.contributor.author | 周慧萍 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:55:27Z | - |
| dc.date.available | 2010-09-09 | |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-30 | |
| dc.identifier.citation | 1. Froland A, Holst G, Terslev E: Multiple anomalies associated with an extra small autosome. Cytogenetics 2:99–106 (1963).
2. Crolla JA, Howard P, Mitchell C, Long FL, Dennis NR: A molecular and FISH approach to determining karyotype and phenotype correlations in six patients with supernumerary marker(22) chromosomes. Am J Med Genet 72:440–447 (1997). 3. Paoloni-Giacobino A, Morris MA, Dahoun SP: Prenatal supernumerary r(16) chromosome characterized by multiprobe FISH with normal pregnancy outcome. Prenat Diagn 18:751–752 (1998). 4. Crolla JA, Long F, Rivera H, Dennis NR: FISH and molecular study of autosomal supernumerary marker chromosomes excluding those derived from chromosomes 15 and 22. I. Results of 26 new cases. Am J Med Genet 75:355–366 (1998). 5. Warburton D: De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet 49: 995–1013 (1991). 6. Hook EB, Cross PK: Extra structurally abnormal chromosomes (ESAC) detected at amniocentesis: frequency in approximately 75,000 prenatal cytogenetic diagnoses and associations with maternal and paternal age. Am J Hum Genet 40:83–101 (1987). 7. ISCN 2005: An International System for Human Cytogenetic Nomenclature, Mitelman F (ed) (S. Karger, Basel 2005). 8. Wolff DJ, Schwartz S: Characterization of Robertsonian translocations by using fluorescence in situ hybridization. Am J Hum Genet 50:174–181 (1992). 9. Bartels I, Schlueter G, Liehr T, von Eggeling F, Starke H, Glaubitz R, Burfeind P: Supernumerary small marker chromosome (SMC) and uniparental disomy 22 in a child with confined placental mosaicism of trisomy 22: trisomy rescue due to marker chromosome formation. Cytogenet Genome Res 101:103–105 (2003). 10. Daniel A, Malafiej P: A Series of supernumerary small ring marker autosomes identified by FISH with chromosome probe arrays and literature review excluding chromosome 15. Am J Med Genet 117A:212–222 (2003). 11. Schreck RR, Breg WR, Erlanger BF, Miller OJ: Preferential derivation of abnormal human G-group-like chromosomes from chromosome 15. Hum Genet 36:1–12 (1977). 12. Mukherjee AB, Murty VV, Rodriguez E, Reuter VE, Bosl GJ, Chaganti RS: Detection and analysis of origin of i(12p), a diagnostic marker of human male germ cell tumors, by fluorescence in situ hybridization. Genes Chromosomes Cancer 3: 300–307 (1991). 13. Choo KH: Centromere DNA dynamics: latent centromeres and neocentromere formation. Am J Hum Genet 61:1225–1233 (1997). 14. Schuffenhauer S, Kobelt A, Daumer-Haas C, Loffler C, Muller G, Murken J, Meitinger T: Interstitial deletion 5p accompanied by dicentric ring formation of the deleted segment resulting in trisomy 5p13-cen. Am J Med Genet 65:56–59 (1996). 15. Stavropoulou C, Mignon C, Delobel B, Moncla A, Depetris D, Croquette MF, Mattei MG: Severe phenotype resulting from an active ring X chromosome in a female with a complex karyotype: characterization and replication study. J Med Genet 35:932–938 (1998). 16. Michalski K, Rauer M, Williamson N, Perszyk A, Hoo JJ: Identification, counselling, and outcome of two cases of prenatally diagnosed supernumerary small ring chromosomes. Am J Med Genet 46:88–94 (1993). 17. Fang YY, Eyre HJ, Bohlander SK, Estop A, McPherson E, Trager T, Riess O, Callen DF: Mechanisms of small ring formation suggested by the molecular characterization of two small accessory ring chromosomes derived from chromosome 4. Am J Hum Genet 57:1137–1142 (1995). 18. Shaikh TH, Budarf ML, Celle L, Zackai EH, Emanuel BS: Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families. Am J Hum Genet 65:1595–1607 (1999). 19. Trifonov V, Fluri S, Binkert F, Nandini A, Anderson J, Rodriguez L, Gross M, Kosyakova N, Mkrtchyan H, Ewers E, Reich D, Weise A and Liehr T: Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated. Mol Cytogenetics 1:6 (2008) 20. Liehr T, Claussen U, Starke H: Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res 107:55–67 (2004) 21. Blennow E, Bui TH, Kristoffersson U, Vujic M, Anneren G, Holmberg E, Nordenskjold M: Swedish survey on extra structurally abnormal chromosomes in 39105 consecutive prenatal diagnoses: prevalence and characterization by fluorescence in situ hybridization. Prenat Diagn 14:1019–1028 (1994). 22. Brondum-Nielsen K, Mikkelsen M: A 10-year survey, 1980–1990, of prenatally diagnosed small supernumerary marker chromosomes, identified by FISH analysis. Outcome and follow-up of 14 cases diagnosed in a series of 12,699 prenatal samples. Prenat Diagn 15:615–619 (1995). 23. Anderlid BM, Sahlen S, Schoumans J, Holmberg E, Ahsgren I, Mortier G, Speleman F, Blennow E: Detailed characterization of 12 supernumerary ring chromosomes using micro-FISH and search for uniparental disomy. Am J Med Genet 99:223–233 (2001). 24. Liehr T: Familial small supernumerary marker chromosomes are predominantly inherited via the maternal line. Genet Med 8: 459-462 (2006). 25. Liehr T, Weise A: Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med 19: 719-731 (2007). 26. Steinbach P, Djalali M: Ineffectivity of accessory bisatellited marker chromosomes in inducing meiotic nondisjunction. Hum Genet 64:402–403 (1983). 27. Liehr T, Mrasek K, Weise A: small supernumerary marker chromosomes progress towards a genotype-phenotype correlation. Cytogenet Genome Res 112: 23-34 (2006). 28. Eggermann T, Schubert R, Engels H, Apacik C, Stengel-Rutkowski S, Haefliger C, Emiliani V, Ricagni C, Schwanitz G: Formation of supernumerary euchromatic short arm isochromosomes: parent and cell stage of origin in new cases and review of the literature. Ann Genet 42:75–80 (1999). 29. Shaikh TH, Budarf ML, Celle L, Zackai EH, Emanuel BS: Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families. Am J Hum Genet 65:1595–1607 (1999) 30. Rineer S, Finucane B, Simon EW: Autistic symptoms among children and young adults with isodicentric chromosome 15. Am J Med Genet 81:428–433 (1998). 31. Roberts SE, Maggouta F, Thomas NS, Jacobs PA, Crolla JA: Molecular and fluorescence in situ hybridization characterization of the breakpoints in 46 large supernumerary marker 15 chromosomes reveals an unexpected level of complexity. Am J Hum Genet 73:1061–1072 (2003). 32. Patsalis PC, Sismani C, Hadjimarcou MI, Kitsiou-Tzeli S, Zera C, Syrrou M, Lyberatou E, Tsezou A, Galla A, Skordis N: Detection and incidence of cryptic Y chromosome sequences in Turner 症候群 patients. Clin Genet 53:249–257 (1998). 33. Kotzot D: small supernumerary marker chromosomes(SMC) and uniparental disomy (UPD): coincidence or consequence? J Med Genet 39:775–778 (2002). 34. Speicher MR, Gwyn Ballard S, and Ward DC: Karyotyping human chromosomes by combinational multi-fluor FISH. Nat Genet 12, 368-375(1996). 35. Schrock E, du Manoir S, Veldman T, Schoell B, Wienberg J, Ferguson-Smith MA, Ning Y, Ledbetter DH, Bar-Am I, Soenksen D, Garini Y, and Ried T: Multicolor spectral karyotyping of human chromosomes. Science 273, 494-497(1996). 36. Langer S., Fauth C., Rocchi M., Murken J. and Speicher M.R: AcroM fluorescent in situ hybridization analyses of marker chromosomes. Hum. Genet. 109, 152-158(2001). 37. Starke H., Heller A., Weise A., Nietzel A., Claussen U. and Liehr T: A new subcentromeric probe set for the characterization of centromere-near rearrangements. Medgen. 14, 262. Abstract(2002). 38. Fung J., Weier H.U., Goldberg J.D. and Pedersen R.A.: Multilocus genetic analysis of single interphase cells by spectral imaging. Hum. Genet. 107, 615-622(2000). 39. Pinkel, D., Segraves, R., Sudar, D., Clark, S., Poole, I.,Kowbel, D., Collins, C., Kuo,W.L., Chen, C., Zhai, Y., et al.: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat. Genet. 20, 207–211(1998). 40. Wang NJ, Liu D, Parokonny AS, Schanen NC: High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage. Am J Hum genet. 75, 267-281(2004). 41. Bühler EM, Méhes K, Müller H, Stalder GR: 'Cat-eye syndrome a partial trisomy 22'. Humangenetik 15 (2): 150–62(1972).. 42. Temtamy SA, Kamel AK, Ismail S, Helmy NA, Aglan MS, El Gammel M, El Ruby M, Mohamed AM: Phenotypic and cytogenetic spectrum of 9p trisomy. Genet Couns 18(1):29-48(2007) 43. Battaglia A: The inv dup (15) or idic (15) syndrome (Tetrasomy 15q). Orphanet Journal of Rare Diseases. 3:30 (2008) 44. Thomas JA, Johnson J, Peterson Kraai TL, et al: Genetic and clinical characterization of patients with an interstitial duplication 15q11- q13, emphasizing behavioral phenotype and response to treatment. Am J Med Genet. 119, 111-120 (2003) 45. Baker P, Piven J, Schwartz S, Patil S: Brief Report: Duplication of chromosome 15q11-13 in two individuals with autistic disorder. J Autism Dev Disord 24:529–535(1994). 46. Gruchy N, Lebrun M, Herlicoviez M, Alliet J, Gourdier D, Kottler M L, Mittre H, Leporrier N: Supernumerary marker chromosomes management in prenatal diagnosis. Am J Med Genet Part A 146A:2770-2776(2008). 47. Freeman, J.L. et al. Copy number variation: New insights into genome diversity. Genome Res. 16, 949–961 (2006). 48. Robinson WP, Barrett IJ, Bernard L, et al.: 'Meiotic origin of trisomy in confined placental mosaicism is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction'. American Journal of Human Genetics 60 (4): 917–27 (1997).. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46144 | - |
| dc.description.abstract | 一般而言，正常人類細胞有46條染色體，但目前世界上大約有三百萬人有多出來的一條或多條小而結構異常的染色體，我們稱這多出來的染色體為small supernumerary marker chromosome (sSMC)，簡稱標記染色體(marker chromosome)。這些結構異常的染色體其大小必須小於等於20號染色體，且單獨以傳統細胞遺傳學染色的方法是無法辨識的。標記染色體雖然早於1961年就被發現，但因他可能來自任何一條染色體的任何部位，因此對於他的特性始終缺乏完整的相關研究，加上標記染色體對表現型的影響變異非常大，因此造成臨床診斷上遺傳諮詢時的困難。
標記染色體於臨床遺傳諮詢時因缺乏良好的診斷工具，因此多是以標記染色體是否是遺傳自父母，以此做為決定是否繼續懷孕的判斷標準。但這樣的判斷準則並不能真正滿足父母的需求，因此本研究收集臨床上細胞遺傳學染色體分析發現帶有標記染色體病人之羊水或血液檢體，以分析全基因組基因劑量變化且解析度更高的晶片式全基因體定量分析技術來進行分析，探討標記染色體的染色體來源、基因組成及其與個案臨床表現之間的關係，以評估臨床上運用晶片式全基因體定量分析技術來分析標記染色體的可行性。 於臨床收集13個於細胞遺傳學染色體分析發現帶有標記染色體病人之細胞檢體，以晶片式全基因體定量分析技術分析結果發現，7個個案基因劑量有明顯的增加，而其中4個已出生之個案都有明顯的臨床症狀，且分析其標記染色體的基因組成，發現皆帶有致病基因；另3個為產前檢查之個案，經將晶片式全基因體定量分析技術分析的結果與個案諮詢後，其中2個個案因其標記染色體帶有基因故選擇終止妊娠，另一位因增加之染色體片段屬正常變異故繼續懷孕，小孩出生後至今無發現異常表現型。 有6個個案無基因劑量變化，推測其標記染色體為來自無探針設計之中心粒或異染色質。其中5個個案已出生，至今皆無明顯的異常症狀；一個為產前檢查之個案，經結果諮詢後因個人因素選擇終止妊娠，但觀察其流產物外觀為正常。 這樣的分析結果顯示運用晶片式全基因體定量分析技術來分析標記染色體，於已出生之個案部分，分析結果可清楚解釋個案之臨床症狀。在產前診斷部分，只要搭配適當的結果判讀及遺傳諮詢，可提供有用的資訊以降低孕婦生出異常胎兒的風險，提昇孕婦繼續懷孕的意願。不失為標記染色體臨床診斷的利器。 | zh_TW |
| dc.description.abstract | In general, normal human cells have 46 chromosomes. But there are about 300 million people in the world have one or more smaller structural abnormalities of chromosomes. These chromosomes are unrecognized by traditional cytogenetic staining method. We call this the extra chromosome marker chromosome. When the marker chromosome is smaller than the size of the chromosome 20. It is called small supernumerary marker chromosome (sSMC)
Early marker chromosome was found in 1961. But it may come from any part of any one chromosome. Therefore the characteristics of this chromosome research has always been lack of. Marker chromosome effects on the phenotype. have very large variation. Resulting difficulties in clinical diagnosis and genetic counseling. Due to the lack of good diagnostic tools for marker chromosome in clinical genetic counseling. Therefore, the criterion of whether to continue pregnancy is depend on whether the marker chromosome is inherited from parents. But this criterion can not really meet the needs of parents, Therefore, this study collected clinical cytogenetic chromosome analysis of amniotic fluid of patients with marker chromosomes or blood samples. Use the analysis technique “array comparative genomic hybridization “which can detect genome-wide changes in gene dose by higher-resolution to explore the origin of the chromosome marker chromosomes, gene composition and with the relationship between clinical manifestations of cases to assess the clinical application of array comparative genomic hybridization to analyze the marker chromosomes feasibility. Collection of 13 clinical cytogenetic chromosome analysis at the marker chromosome with the cell samples of patients. Using array comparative genomic hybridization analysis and the results was found, 7 cases of genes could significantly increase, of which four cases of birth have clear clinical symptoms, we analyze the genetic composition of marker chromosomes, disease gene were found. The other three are prenatal cases. After the array comparative genomic hybridization analysis and case consultation, the composition of two case’s marker chromosomes have euchromatin so they choose to terminate the pregnancy. Another case has increased chromosome segment is copy number variation, which is normal, so continue her pregnancy, child birth has no abnormal presentation. 6 cases no change in gene dosage, we speculated that the marker chromosome maybe from the centromere or heterochromatin. Of which five cases have been born, so far have no obvious abnormalities. One case of prenatal exam choose to terminate pregnancy due to personal reasons, however observation and appearance fetus is normal. This study showed that the use of array comparative genomic hybridization to analyze the marker chromosome. In some cases that have been born. The results may explain the clinical symptoms of the case. In the prenatal diagnosis, with appropriate interpretation and genetic counseling, Can provide useful information to reduce the risk of pregnant women give birth to abnormal fetuses and improve the wish of pregnant women to continue pregnancy. Is also a good clinical diagnostic tool for marker chromosome. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:55:27Z (GMT). No. of bitstreams: 1 ntu-99-P97448009-1.pdf: 1723437 bytes, checksum: 7ce6e00d617182b1e1fec053c1c3d914 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 口試委員會審定書………………………………………………..…………………..…i
誌謝………………………………………………..………………………………...……ii 中文摘要…………………………………………………..……………………………iii英文摘要 ………………………………………………..……………………………….v 第一章 緒論…………………………………………………………………………...…1 1.1 標記染色體之簡介 …………………………………………………………..…1 1.2 標記染色體的命名與定義……………………..………………………..…....…1 1.3 標記染色體的形成..………………………………………..………………....…2 1.4 來自acrocentrics和non-acrocentrics 的標記染色體的分布比例……………..5 1.5 標記染色體的家族遺傳率及鑲嵌型比例..…………………………..………....5 1.6 標記染色體的發現比例..…………………………………………..……………6 1.7 標記染色體與單親源雙倍體………………….………………………..……….8 1.8 標記染色體之診斷方法與臨床運用.………………………………….…….….8 1.9 研究動機……………………………………………..…………...…….…….…10 第二章 實驗材料與儀器…………………………………………………..…...…….....12 2.1 實驗材料與試劑…………………………………………...…..……….……..…12 2.1.1標記染色體基因檢測之DNA檢體……..………………………………..12 2.1.2 BAC Array CGH 晶片……………………………………………....…….12 2.1.3 Oligo array CGH晶片………………………………………..………....…12 第三章 實驗方法……………………………………………………………......…....…13 3.1 萃取DNA……………………………………………………….…….…...……13 3.2 晶片式全基因體定量分析技術………………………………….…...…....……13 第四章 實驗結果……………………………………………………...………...........…14 4.1 本次實驗帶有標記染色體個案的基本資料…................…..…...............…......14 4.2 本次實驗標記染色體的統計資料…………………………………...…..…....19 第五章 討論………………………………………………………………….…......…20 第六章 結論………………………………………………………………….…..........25 第七章 參考文獻………………………………………………...……………...….…26 圖目錄 圖一 標記染色體的型態….………………………………………..……...………...32 圖二 U形交換(U-type exchange)……………..………………………………….....33 圖三 形成環狀標記染色體的假說機制…………………………..………..…….…34 圖四 標記染色體以傳統細胞遺傳學染色體染色方法分析時的遺傳諮詢準則….35 圖五 自發性突變產生標記染色體產前診斷的困境………..……………………...36 圖六A 個案1之理學檢查…………….…………………………………………… 37 B 個案1染色體圖譜(47,XX.+mar) …………….……………………...……. 37 C個案1之aCGH檢查結……………………………..…………………….… 37 圖七A 個案2染色體圖譜(47,XX.+mar) ………………….……..…………..….…38 B 個案2之aCGH檢查結果……………………..………………………….…38 圖八A 個案3染色體圖譜(47,XY.+mar) …………………..……..………………...39 B 個案3之aCGH檢查結果……………………..………………………….…39 圖九 個案4之aCGH檢查結果……………………………..…………….………...40 圖十 個案5之aCGH檢查結果……………………………..………….…….…..…41 圖十一 A 個案6染色體圖譜(47,XY.+mar) …………….…………..……….…...…42 B 個案6之oligo aCGH檢查結果…………..…...…………………......…42 圖十二 A 個案7染色體圖譜(47,XY +mar[9]/46,XY[11] )……..…………….....…43 B 個案7之aCGH檢查結果………………..……………….………..…….43 圖十三 A 個案8染色體圖譜(47,XY +mar[27]/46,XY[23]) ………………..………44 B 個案8之aCGH檢查結果………………………..…………………..…44 圖十四 A 個案9染色體圖譜(47,XY.+mar) ……………………….………….…….45 B 個案9之aCGH檢查結果………………………..………………………45 圖十五 A 個案10染色體圖譜48,XY +mar1,+mar2 ………….……………..…46 B 個案10之aCGH檢查結果…….…………………………………….47 圖十六 A 個案11染色體圖譜(47,XX.+mar) ……………………..……………48 B 個案11之aCGH檢查結果………………………………….…….…48 C 個案11之父的染色體圖譜46,XY,t(6;22)(p22;q12) ………………...49 圖十七 A 個案12染色體圖譜mos 47,XX +mar[6]/46,XX[8]..……….…….…50 B 個案12之aCGH檢查結果………………………...……..……...….50 圖十八 A 個案13染色體圖譜(47,XY+mar) ……………………..……..……....51 B 個案13之aCGH檢查結果………………………………………….51 圖十九 標記染色體導致單親緣雙倍體的機制.…….………………….………...52 圖二十標記染色體產前診斷的建議流程…………….……………………….…..53 表目錄 表一 標記染色體的統計資料…………………………….………………………54 | |
| dc.language.iso | zh-TW | |
| dc.title | 晶片式比較基因體雜交技術於臨床診斷標誌染色體之應用 | zh_TW |
| dc.title | Application of array comparative genomic hybridization for clinical diagnosis of small supernumerary marker chromosome | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳持平,李建南 | |
| dc.subject.keyword | 標記染色體,產前檢查,晶片式全基因體定量分析技術, | zh_TW |
| dc.subject.keyword | marker chromosome,array comparative genomic hybridization,prenatal diagnosis, | en |
| dc.relation.page | 54 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-07-30 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-99-1.pdf 目前未授權公開取用 | 1.68 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。