Cell-based non-invasive prenatal testing: circulating trophoblast enrichment and genetic analysis.

Weymaere, Jana
Faculteit Farmaceutische Wetenschappen
Vakgroep Geneesmiddelenleer
Master in Drug development, Universiteit Gent, 2015-2017 Bachelor in Pharmaceutical Sciences, Universiteit Gent, 2012-2015
Academische graad
Doctor in de farmaceutische wetenschappen
Taal proefschrift
Vertaling titel
Cel-gebaseerd niet-invasief prenataal testen: aanrijking van circulerende trofoblasten en genetische analyse.
Prof. dr. Dieter Deforce, UGent-Geneesmiddelenleer - Prof. dr. Filip Van Nieuwerburgh, UGent-Geneesmiddelenleer
Prof. dr. Kevin Braeckmans, UGent-Geneesmiddelenleer - Prof. dr. Marthe De Boevre, UGent-Bioanalyse - Prof. dr. Bart Broeckx, UGent-Faculteit Diergeneeskunde-Vakgroep Voeding, Genetica en Ethologie - Prof. Dr. Ward De Spiegelaere, UGent-Faculteit Diergeneeskunde-Vakgroep Morfologie - Prof. Dr. Kathleen Claes, UGent-Faculteit Geneeskunde en Gezondheidswetenschappen-Vakgroep Biomoleculaire Geneeskunde - Prof. Dr. Liesbet Lagae, KU Leuven–Departement Natuurkunde en Sterrenkunde

Korte beschrijving

Many attempts have been made worldwide to isolate and analyze circulating trophoblasts (CTs) in maternal blood for cell-based non-invasive prenatal testing (cbNIPT). Despite extensive academic and commercial research efforts, it has not yet been possible to develop a routine clinical cbNIPT. This dissertation aims to contribute to the development of cbNIPT by optimizing the fetal identity confirmation step and by investigating novel technologies for CT enrichment. First, in order to optimize the fetal identity confirmation step, the efficacy and evidential value of two genotyping methods are compared for the offspring-parent discrimination of single cells after whole genome amplification. These two methods include short tandem repeat genotyping based on capillary electrophoretic detection and single nucleotide polymorphism genotyping using next generation sequencing. Within each genotyping method, both unfixed and formaldehyde-fixed single cells are tested in offspring-parent duos and offspring-mother-father trios. The results demonstrate that both short tandem repeat genotyping and single nucleotide polymorphism genotyping allow offspring versus parent discrimination of single cells after WGA with 100% sensitivity and 100% specificity, but single nucleotide polymorphism genotyping results in a higher evidential value. Second, two novel enrichment technologies are investigated for their potential of enriching CTs. Results demonstrate that the Metacell technology, which is a novel filtration-based technology for enrichment of larger cells from whole blood, is not suitable for consistent CT enrichment. On the contrary, the Vortex technology, which enriches larger cells from whole blood by exploiting inertial microfluidics and laminar microscale vortices, seems promising based on this proof-of-concept study.


Donderdag 2 december 2021, 18:00
Faculteit Farmaceutische Wetenschappen - Auditorium B - Andreas Vesalius, Ottergemsesteenweg 460, 9000 Gent
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