本文選題：胎兒性別鑒定　切入點：孕婦血漿測序　出處：《華南理工大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的——開發(fā)一種基于孕婦血漿測序的胎兒性別鑒定方法，評價其作為篩檢試驗的可能性，及其在性連鎖遺傳病咨詢中的應(yīng)用潛能。 方法——選取900例孕周為12-16周的、已知出生隨訪結(jié)果的孕婦血漿測序數(shù)據(jù)進行回顧性分析，其中訓(xùn)練集和驗證集分別為100例和800例。統(tǒng)計比對到Y(jié)染色體上的測序片段的百分比，，基于ROC曲線方法選取性別鑒定分界值，并用于鑒定胎兒性別。招募8例杜氏肌營養(yǎng)不良癥的攜帶者孕婦進行同步盲法測試，通過孕婦血漿測序，利用所建立的方法進行胎兒性別鑒定。對性別鑒定錯誤樣本進行全面的回顧分析，包括常染色體數(shù)目異常檢測及臨床記錄。其中，常染色體數(shù)目異常檢測通過建立引入內(nèi)部參考染色體的Z檢驗方法進行。 結(jié)果——在訓(xùn)練集中，本方法對胎兒性別鑒定的靈敏度和假陽性率分別為96%和0%。在驗證集中，423例男胎中421例成功鑒別，377例女胎中374例成功鑒別，靈敏度及特異性達到99.53%和99.20%，其余各項評估指標(biāo)均達到篩檢試驗要求。與羊水穿刺金標(biāo)準(zhǔn)對比，8例杜氏肌營養(yǎng)不良癥攜帶者的胎兒性別鑒定均正確。引入內(nèi)部參考染色體的Z檢驗方法對T13、T18和T21的檢測靈敏度為100%，特異性為98.7%，100%和100%。使用該方法篩查所有5例性別鑒定錯誤樣本，結(jié)果均為陰性。另外，該錯誤樣本與孕周、孕婦年齡、唐氏風(fēng)險和妊娠異常病史均沒有直接關(guān)系。 結(jié)論——基于孕婦血漿測序，無創(chuàng)性的胎兒性別鑒定可達到高準(zhǔn)確率。本方法在具有完善的倫理學(xué)考量的前提下，具有產(chǎn)前遺傳咨詢的應(yīng)用前景。
[Abstract]:Objective to develop a method of fetal sex identification based on maternal plasma sequencing and to evaluate the possibility of screening test and its potential application in sex-linked genetic disease counseling. Methods the plasma sequencing data of 900 pregnant women aged 12-16 weeks with known birth follow-up results were retrospectively analyzed. The training set and validation set were 100 cases and 800 cases, respectively. The percentage of sequenced fragments on Y chromosome was statistically compared, and the gender identification boundary value was selected based on ROC curve method. It was used to identify fetal sex. Eight pregnant women with Duchenne muscular dystrophy were recruited for simultaneous blind test, and their plasma was sequenced. Using the established method for fetal sex identification. A comprehensive retrospective analysis of the wrong sex identification samples, including the detection of autosomal abnormalities and clinical records. The detection of autosomal abnormalities was carried out by establishing a Z test with internal reference chromosomes. Results in the training concentration, the sensitivity and false positive rate of this method for fetal sex identification were 96% and 0 respectively. Among 423 cases of male fetus, 421 cases were successfully identified from 377 cases of female fetus and 374 cases of female fetus were successfully identified. The sensitivity and specificity reached 99.53% and 99.20%, and the other evaluation indexes met the requirements of screening test. Compared with the gold standard of amniotic fluid puncture, the fetal sex identification of 8 cases with Duchenne muscular dystrophy was correct. The sensitivity and specificity of the Z method for the detection of T13, T18 and T21 were 100, 98.7% and 100%, respectively. The results were all negative. In addition, there was no direct relationship between the false sample and gestational age, age of pregnant women, Down's risk and history of abnormal pregnancy. Conclusion-based on maternal plasma sequencing, noninvasive fetal sex identification can achieve high accuracy. This method has the application prospect of prenatal genetic counseling on the premise of perfect ethical considerations.
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R714.5


本文編號：1648514