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Title: Transcriptomic and proteomic analysis of placenta tissue : application to non-invasive prenatal diagnosis and screening of Down’s syndrome
Author: Choi, Kin
ISNI:       0000 0004 2727 4546
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
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Prenatal diagnosis of Down's syndrome (OS) requires a invasive procedure to obtain samples for analysis using a diagnostic test but the invasive procedure could lead to miscarriage. This study aimed to identify RNA transcript and protein markers for OS which are present in maternal plasma and serum for. use in a non-invasive prenatal diagnostic (NIPO) or non- invasive prenatal screening (NIPS) test for OS. Affymetrix Human Genome U133 plus 2.0 Arrays and 2-dimensional difference gel electrophoresis (2-D OIGE) were used to provide whole genome and proteome analysis of RNA transcript and protein abundances between first trimester euploid and OS placenta samples. Placenta tissue was used because it contains fetal cells. Reverse transcription real-time polymerase chain reaction (RT R- T peR) was used to validate the amounts of some of the candidate RNA transcripts. The 2-D OIGE experiments found transglutaminase 2 protein present in lower amounts in OS placenta compared to euploid placenta. Furthermore, transglutaminase 2 is suitable for further analysis as a protein target in a quantitative NIPS test for OS because there are low levels of expression of TGM2 in maternal tissues relative to fetal and maternal tissues and therefore TGM2 could be affected only very slightly by the 'masking effect'. The results from the microarray experiment provided evidence of a 45.6% fold increase in expression of genes located in chromosome 21 in the OS samples compared to the euploid samples which is evidence of the 'primary gene dosage effect'. The primary gene dosage effect proposes a 50% increase in expression from genes located in chromosome 21 in OS tissue as a consequence of the 50% increase in the number of copies of chromosome 21 in the cells of the OS tissue. A bioinformatic approach was also used to identify SNPs for use in the RNA-SNP strategy for NIPS of OS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available