Prenatal diagnosis is an established obstetrics practice in many countries. Currently available methods to obtain fetal materials for a definitive diagnosis involve invasive procedures such as chorionic villus sampling and amniocentesis. Due to the invasive nature of the procedures, confirmatory testing is usually recommended only for pregnant women who are screened as being high risk of bearing a fetus with abnormalities. There has been an urge to develop safer alternatives in obtaining fetal genetic materials for prenatal assessment. Thus, the discovery of circulating fetal DNA in maternal plasma and serum has opened up new possibilities for noninvasive prenatal diagnosis. / The use of genetic markers such as Y chromosomal sequences from a male fetus or paternally-inherited polymorphic markers has been well-described in the literature. However, there is an obvious limitation on the use of these markers because they are gender- and/or polymorphism-dependent. This thesis focuses on the development of a universal fetal marker, namely SERPINB5 (encoding maspin), based on the intrinsic epigenetic differences between the placenta (the major contributor of fetal genetic materials in maternal plasma) and maternal blood cells (postulated to be the predominant source of cell-free DNA in the circulation). Analysis of the methylation profile of the SERPINB5 promoter in the placenta and maternal blood cells, and the development of methods and protocols to detect the differentially methylated SERPINB5 promoter molecules are described. The application of this epigenetic marker in prenatal assessment of the fetal chromosomal aneuploidy is illustrated by an epigenetic allelic ratio (EAR) approach. Basically, the ratio of a single-nucleotide polymorphism (SNP) on the placenta-derived SERPINB5 molecules is shown to be deviated in the maternal plasma from trisomic pregnancies when compared to the euploid ones. Results described in this thesis show the promising potential for the EAR approach for the noninvasive prenatal detection of fetal chromosomal aneuploidies. In addition, a novel approach for methylation analyses on the amplification and detection of restriction enzyme-digested DNA fragments will be discussed. This thesis has essentially described the evolution of a fetal epigenetic marker from basic science to potential clinical application. / Tong, Yu Kwan. / Adviser: Yuk-Ming Dennis Lo. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0953. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 149-172). / 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. / Abstract also in Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344438 |
| Date | January 2007 |
| Contributors | Tong, Yu Kwan., 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 (xix, 172 leaves : 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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