Circulating RNA offers a new detection approach for non-invasive diagnosis. Over the past few years, much effort has been spent on the investigation of possible detection of circulating RNA in plasma. In this thesis, we aim to quantify and characterize cell-free RNA in plasma, and investigate the possibility of using circulating fetal RNA in maternal plasma for non-invasive prenatal diagnosis or monitoring. / In the first part of the thesis, the particle-associated nature of circulating RNA was investigated. Quantitative real-time reverse-transcriptase polymerase chain reaction was developed to measure circulating RNA in healthy individuals and hepatocellular carcinoma (HCC) patients. By subjecting plasma samples to filtration and ultracentrifugation, the presence of both particle-associated and non-particle-associated mRNA species was demonstrated in human plasma. In HCC patents, both the circulating particle- and non-particle-associated plasma RNA concentrations were increased. / The discovery of circulating nucleic acids in plasma and serum has led to the development of numerous promising non-invasive diagnostic tests. The initial non-invasive tests mainly target circulating DNA species. For prenatal diagnosis, circulating fetal DNA in maternal plasma has been utilized for the non-invasive determination of a number of fetal genetic traits. However, as fetal and maternal DNA species co-exist in maternal plasma, these DNA based diagnostic applications depend largely on the use of genetic markers that could discriminate between fetal and maternal DNA, such as the Y chromosome of a male fetus. Thus, a particular DNA marker could only be used in a proportion of pregnancies. This limitation has prompted a quest to develop new fetal nucleic acid markers that are independent of sex or polymorphism and that can be used in all pregnancies. / The existence of circulating RNA is an extraordinary finding because RNA is more labile than DNA and ribonuclease is known to be present in blood. The second study of the thesis reveals that circulating RNA is surprisingly stable under different preanalytical situations. This information has made the study of circulating RNA simpler and more practical for clinical uses. / The third part of this thesis aims at detecting circulating fetal RNA in the plasma of pregnant women. We showed that two placental-derived mRNA species, namely those transcribed from the genes coding for human placental lactogen (hPL) and the beta-subunit of human chorionic gonadotropin (betahCG), are readily detectable in maternal plasma. (Abstract shortened by UMI.) / Tsui Bo Yin. / "May 2005." / Adviser: Y. M. Dennis Lo. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0074. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 166-189). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343624 |
| Date | January 2005 |
| Contributors | Tsui, Bo Yin., Chinese University of Hong Kong Graduate School. Division of Chemical Pathology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xviii, 189 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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