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Abstract

This thesis is focused on the study of the biology and pathobiology of circulating non-host cell-free DNA in human plasma and serum. For the purpose of the thesis, "non-host" DNA represents any DNA species which has detectable sequence difference from the germline DNA of the host.

The first non-host DNA type studied was circulating fetal DNA that was found in the plasma and serum of pregnant women. The work presented in this thesis represented the first demonstration of the existence of circulating fetal DNA in the cell-free fraction of maternal blood. The use of real time quantitative polymerase chain reaction (PCR) allowed the measurement of circulating fetal DNA concentrations at different stages of pregnancy, with an increase in fetal DNA concentration with progress in gestation. The study of pathological pregnancies indicated that women with preeclampsia and preterm labour had higher levels of circulating fetal DNA than those not suffering from these disorders. These findings might have implication for the potential use of plasma DNA for diagnosing or monitoring these common pregnancy-associated disorders. The applicability of maternal plasma DNA analysis to non-invasive prenatal diagnosis was studied using fetal rhesus D status determination as a model system. Using this system, it was shown that the rhesus D status of fetuses carried by rhesus-negative pregnant women could be reliably determined by DNA analysis of maternal plasma samples from the second trimester onwards.

The second non-host DNA type studied was circulating donor-derived DNA that was found in the plasma of liver and kidney transplant recipients. The third non-host DNA type studied was circulating tumour-associated DNA that was found in the plasma of cancer patients.

Details

Title
Molecular analysis of non-host cell-free dna in human plasma and serum
Author
Lo, Yuk-Ming Dennis
Year
2000
Publisher
ProQuest Dissertations & Theses
Source type
Dissertation or Thesis
Language of publication
English
ProQuest document ID
301566813
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.