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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 謝豐舟(Fon-Jou Hsieh) | |
| dc.contributor.author | Sheng-Wen Shaw | en |
| dc.contributor.author | 蕭勝文 | zh_TW |
| dc.date.accessioned | 2021-06-13T02:02:07Z | - |
| dc.date.available | 2007-08-08 | |
| dc.date.copyright | 2007-08-08 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-07 | |
| dc.identifier.citation | 1 Lejeune J, Gautier M, Turpin R: [Study of somatic chromosomes from 9 mongoloid children.]. C R Hebd Seances Acad Sci 1959; 248: 1721-1722.
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Gene 2003; 312: 41-50. 18 Tapparel C, Reymond A, Girardet C et al: The TPTE gene family: cellular expression, subcellular localization and alternative splicing. Gene 2003; 323: 189-199. 19 Pinkel D, Segraves R, Sudar D et al: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 1998; 20: 207-211. 20 Pollack JR, Perou CM, Alizadeh AA et al: Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat Genet 1999; 23: 41-46. 21 Snijders AM, Nowak N, Segraves R et al: Assembly of microarrays for genome-wide measurement of DNA copy number. Nat Genet 2001; 29: 263-264. 22 Greshock J, Naylor TL, Margolin A et al: 1-Mb resolution array-based comparative genomic hybridization using a BAC clone set optimized for cancer gene analysis. Genome Res 2004; 14: 179-187. 23 Hodgson G, Hager JH, Volik S et al: Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas. 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Birth Defects Res A Clin Mol Teratol 2006; 76: 739-743. 29 Antonarakis SE, Adelsberger PA, Petersen MB, Binkert F, Schinzel AA: Analysis of DNA polymorphisms suggests that most de novo dup(21q) chromosomes in patients with Down syndrome are isochromosomes and not translocations. Am J Hum Genet 1990; 47: 968-972. 30 Shaffer LG, Jackson-Cook CK, Stasiowski BA, Spence JE, Brown JA: Parental origin determination in thirty de novo Robertsonian translocations. Am J Med Genet 1992; 43: 957-963. 31 Petersen MB, Adelsberger PA, Schinzel AA, Binkert F, Hinkel GK, Antonarakis SE: Down syndrome due to de novo Robertsonian translocation t(14q;21q): DNA polymorphism analysis suggests that the origin of the extra 21q is maternal. Am J Hum Genet 1991; 49: 529-536. 32 Kim SR, Shaffer LG: Robertsonian translocations: mechanisms of formation, aneuploidy, and uniparental disomy and diagnostic considerations. Genet Test 2002; 6: 163-168. 33 Delabar JM, Theophile D, Rahmani Z et al: Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet 1993; 1: 114-124. 34 Valero R, Marfany G, Gil-Benso R et al: Molecular characterisation of partial chromosome 21 aneuploidies by fluorescent PCR. J Med Genet 1999; 36: 694-699. 35 Flint J, Knight S: The use of telomere probes to investigate submicroscopic rearrangements associated with mental retardation. Curr Opin Genet Dev 2003; 13: 310-316. 36 Bruder CE, Hirvela C, Tapia-Paez I et al: High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH. Hum Mol Genet 2001; 10: 271-282. 37 Yu W, Ballif BC, Kashork CD et al: Development of a comparative genomic hybridization microarray and demonstration of its utility with 25 well-characterized 1p36 deletions. Hum Mol Genet 2003; 12: 2145-2152. 38 Shaw CJ, Shaw CA, Yu W et al: Comparative genomic hybridisation using a proximal 17p BAC/PAC array detects rearrangements responsible for four genomic disorders. J Med Genet 2004; 41: 113-119. 39 Vissers LE, de Vries BB, Osoegawa K et al: Array-based comparative genomic hybridization for the genomewide detection of submicroscopic chromosomal abnormalities. Am J Hum Genet 2003; 73: 1261-1270. 40 Sullivan BA, Jenkins LS, Karson EM, Leana-Cox J, Schwartz S: Evidence for structural heterogeneity from molecular cytogenetic analysis of dicentric Robertsonian translocations. Am J Hum Genet 1996; 59: 167-175. 41 Bonthron DT, Smith SJ, Fantes J, Gosden CM: De novo microdeletion on an inherited Robertsonian translocation chromosome: a cause for dysmorphism in the apparently balanced translocation carrier. Am J Hum Genet 1993; 53: 629-637. 42 Earle E, Shaffer LG, Kalitsis P, McQuillan C, Dale S, Choo KH: Identification of DNA sequences flanking the breakpoint of human t(14q21q) Robertsonian translocations. Am J Hum Genet 1992; 50: 717-724. 43 Rogatcheva MB, Ono T, Sonta S, Oda S, Borodin PM: Robertsonian metacentrics of the house musk shrew (Suncus murinus, Insectivora, Soricidae) lose the telomeric sequences in the centromeric area. Genes Genet Syst 2000; 75: 155-158. 44 Finishing the euchromatic sequence of the human genome. Nature 2004; 431: 931-945. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30364 | - |
| dc.description.abstract | 唐氏症是最常見導致智能障礙的疾病，只有百分之四左右的唐氏症屬於羅伯遜轉位型唐氏症。羅伯遜轉位發生在近端著絲粒染色體上，包含了第13，14，15，21和22號染色體。文獻上有幾種機制會產生羅伯遜轉位，最常見的是其中兩條染色體都斷在短臂，然後互相接合，接合後形成兩個中心體的新染色體。除了第21號染色體之外，所有的近端著絲粒染色體在短臂上面都沒有基因分佈。因此我們這個研究目標是當發生羅伯遜轉位時，希望可以找到在第21號染色體短臂上的可能斷點區域。我們從三個醫學中心，前瞻性且連續收集十個羅伯遜轉位型唐氏症患。十個個案中，有六個屬於原發性轉位，另外四個是因為父母親的遺傳。分析起來有四個der(21q;21q)，四個der(14q;21q)，一個der(13q;21q)與一個der(21q;22q)。在六個原發性羅伯遜轉位唐氏症中，五個是母源，只有一個是父源。另外有四個第21號染色體發生接合時, 都是屬於等臂染色體。10K微矩陣比較性基因體雜交技術應用在這十個案例上，發現所有第21號染色體的長臂都有複製，不過並沒有發現任何缺失或增加在其他染色體上。244K微矩陣比較性基因體雜交的解析度更高，在其中一個案例發現偵測21p的基因變化的結果，和即時定量聚合酵素連鎖反應的結果相符合。我們接著應用即時定量聚合酵素連鎖反應偵測每個案例在TPTE和BAGE2上面的基因劑量變化，這兩個基因都位在21p11，另外也偵測位於21q11上面的SAMSN1基因。第21號染色體短臂比長臂的基因拷貝數比例：第21號等臂染色體是1:3，其他三種羅伯遜轉位是2:3。因此，我們初步的研究結果顯示，當第21號染色體發生羅伯遜轉位時，其斷點極有可能介於中心粒與BAGE2之間。 | zh_TW |
| dc.description.abstract | Down syndrome (DS) is the most common single known cause of intellectual disability. Only 4% of DS is Robertsonian translocation (ROB) from acrocentric chromosome rearrangement including chromosome 13, 14, 15, 21 and 22. There are some possible mechanisms of formation of the translocation. Union following breakages in both short arms results in a chromosome with two centromeres. Chromosome 21 is the only acrocentric chromosome that has known genes in short arm. The aim of this study was to define the possible breakage area in 21p when ROB occurs. We prospectively and consecutively collected 10 cases ROB DS from 3 medical centers. Of the 10 DS children, 6 were de novo (60%) and 4 were inheritance (40%). There were 4 der(21q;21q), 4 der(14q;21q), 1 der(13q;21q), and 1 der(21q;22q). The origin of the extra chromosome 21q was maternal in 5 of 6 de novo ROB and was paternal in one case. All of the four der(21q;21q) ROB DS were isochromosome. 10K array comparative genomic hybridization (CGH) was applied to 10 cases that showed the whole long arm amplification in chromosome 21. There was no microscopic nor subtelomeric deletion/duplication in other chromosomes. The result of gene dosage change by real-time quantitative polymerase chain reaction (PCR) was compatible with 244K array CGH in one case. We further used real-time PCR to detect the copy number of TPTE and BAGE2 that located in 21p11, SAMSN1 in 21q11. The ratio of copy number in 21p:21q was 1:3 in der(21q;21q), 2:3 in der(13q;21q), der(14q;21q), and der(21q;22q). Our preliminary results demonstrated breakpoint of chromosome 21 involving ROB might be between BAGE2 and centromere, located from 10.1 Mb to 12.3 Mb. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T02:02:07Z (GMT). No. of bitstreams: 1 ntu-96-P94448006-1.pdf: 2307651 bytes, checksum: f5effc6c7f46bc701e1be2b0f54c4ef7 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | Contents
致謝 摘要 Abstract 1. Introduction 1 1.1. General background of Down syndrome 1 1.2. Three genetic types of Down syndrome 1 1.3. Mechanism of Robertsonian translocation 2 1.4. Two genes in the short arm of chromosome 21 2 1.5. Advantage of array CGH 3 1.6. Aim of our study 3 2. Materials and Method 4 2.1. Case selection 4 2.2. Genomic DNA isolation 5 2.3. Molecular genetic analysis 5 2.4. Human Mapping 10K Array 5 2.5. 244k Array CGH experiment 6 2.6. Image Acquisition and Raw Data Processing. 7 2.7. PCR primers 8 2.8. Real-time Quantitative PCR and Calculation of Gene Dosage 8 3. Result 10 3.1. Parental origin and UPD study 10 3.2. Phenotype of Robertsonian Down syndrome 11 3.3. Result of 10K array CGH 11 3.4. Result of 244K array CGH and real-time PCR in one case 12 3.5. Real-time PCR for gene dosage change 12 4. Discussion 14 4.1. Parental origin of ROB DS and isochromosome 21 14 4.2. UPD study for Robertsonian translocation 14 4.3. Phenotype of ROB DS and free trisomy 21 was similar 15 4.4. Array CGH could detect microscopic changes 15 4.5. 10K array CGH showed whole 21q amplification 16 4.6. Probes of TPTE and BAGE2 on 244K array CGH 16 4.7. Real time PCR showed the breakpoint in 21p 17 4.8. Further studies could be planned in the future 18 5. Conclusion 19 6. Reference 20 7. Legends to figures 28 7.1. Figure 1 to Figure 10 28 7.2. Figure 11 28 7.3. Figure 12 28 7.4. Figure 13 29 7.5. Figure 14 29 8. Figures 30 8.1. Figure 1 30 8.2. Figure 2 31 8.3. Figure 3 32 8.4. Figure 4 33 8.5. Figure 5 34 8.6. Figure 6 35 8.7. Figure 7 36 8.8. Figure 8 37 8.9. Figure 9 38 8.10. Figure 10 39 8.11. Figure 11 40 8.12. Figure 12 41 8.13. Figure 13 42 8.14. Figure 14 43 9. Tables 44 9.1. Table 1. General characteristics of 10 cases Robertsonian Down syndrome 44 9.2. Table 2. The parental origin of 10 cases by informative small tandem repeat (STR) markers 45 9.3. Table 3. Phenotype of 10 cases Robertsonian Down syndrome 46 9.4. Table 4. Real-time PCR verification of gene dosage of TPTE, BAGE2, and SAMSN1 by array-CGH in case 2 47 9.5. Table 5. The result of gene dosage and DNA copy number ratio of 21p:21q by real-time PCR 48 10. Addendum 49 10.1. 台大醫院研究倫理委員會通過證明 49 10.2. 長庚醫院人體試驗倫理委員會通過證明 50 10.3. 長庚醫學研究計畫通過證明 51 10.4. Recent Publication 52 10.5. Research Project 53 | |
| dc.language.iso | en | |
| dc.subject | BAGE2 | zh_TW |
| dc.subject | 羅伯遜轉位 | zh_TW |
| dc.subject | 唐氏症 | zh_TW |
| dc.subject | TPTE | zh_TW |
| dc.subject | BAGE2 | en |
| dc.subject | Robertsonian translocation | en |
| dc.subject | Down syndrome | en |
| dc.subject | TPTE | en |
| dc.title | 羅伯遜轉位型唐氏症在TPTE與BAGE2上的基因劑量變化和斷點分析 | zh_TW |
| dc.title | The Gene Dosage Changes of TPTE and BAGE2 and Breakpoint Analysis in Robertsonian Down syndrome | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 華筱玲(Hsiao-Lin Hwa) | |
| dc.contributor.oralexamcommittee | 陳持平(Chih-Ping Chen),王子豪(Tzu-Hao Wang),侯家瑋(Jia-Woei Hou) | |
| dc.subject.keyword | 羅伯遜轉位,唐氏症,TPTE,BAGE2, | zh_TW |
| dc.subject.keyword | Robertsonian translocation,Down syndrome,TPTE,BAGE2, | en |
| dc.relation.page | 51 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-09 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| Appears in Collections: | 分子醫學研究所 | |
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