https://scholars.lib.ntu.edu.tw/handle/123456789/160172
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 Application of array comparative genomic hybridization for clinical diagnosis of small supernumerary marker chromosome |
Authors: | 周慧萍 Chou, Hui-Ping |
Keywords: | 標記染色體;產前檢查;晶片式全基因體定量分析技術;marker chromosome;array comparative genomic hybridization;prenatal diagnosis | Issue Date: | 2010 | 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。 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. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/247402 |
Appears in Collections: | 分子醫學研究所 |
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ntu-99-P97448009-1.pdf | 23.32 kB | Adobe PDF | View/Open |
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