We performed an innovative systematic meta-analysis of gene expression profiles of whole
normal human brain and heart to provide a quantitative transcriptome reference map of it, i.e. a
typical reference value of expression for all the known, mapped and uncharacterized (unmapped)
transcripts. For this reason, we used the software named TRAM (Transcriptome Mapper), which
is able to generate transcriptome maps based on gene expression data from multiple sources. We
also analyzed differential gene expression by comparing brain with human foetal brain, with a
pool of non-brain tissues and with the three brain sub-region: cerebellum, cerebral cortex and
hippocampus, the main regions severely affected with cognitive impairment, as seen in the case
of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using
TRAM software and validated in vitro by assaying gene expression through several magnitude
orders by "Real Time" reverse transcription polymerase chain reaction (RT-PCR). The excellent
agreement between in silico and experimental data suggested that our transcriptome maps may
be a useful quantitative reference benchmark for gene expression studies related to the human
brain and heart.
We also generated an integrated quantitative transcriptome map by systematic meta-analysis
from all available gene expression profile datasets related to AMKL in paediatric age. The
incidence of Acute Megakaryoblastic Leukemia (AMKL) is 500-fold higher in children with
Down Syndrome (DS) compared with non-DS children. We present an integrated original model
of the DS AMLK transcriptome, providing the identification of genes relevant for its
pathophysiology which can potentially be new clinical markers.
Finally, computational and molecular analysis of a highly restricted region of chromosome
21, which represents a strong candidate for typical DS features and is considered as intergenic,
was performed. Northern Blot analysis and computational biology results show that HR-DSCR
contain active loci bidirectionally transcribed.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:7546 |
| Date | January 1900 |
| Creators | Caracausi, Maria <1985> |
| Contributors | Strippoli, Pierluigi |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/embargoedAccess |
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