A.I. Virtanen Institute
for Molecular Sciences, Department Of Neurobiology,
Laboratory of Function Genomics and Bioinformatics,
Neulaniementie 2, Kuopio 70211, Finland
title:
Synexpression Analysis of ESTs in the Rat Brain
Reveals Distinct Patterns and Potential Drug
Targets
Marvanova M. a, Törönen P. b, Storvik M.
a, Lakso M. a, Castrén E. b, and Wong
G
The gene expression profiles of 146 novel ESTs were
characterized in newborn and adult rat brains via
radioactive in situ hybridization. Using Euclidian
metrics and hierarchical clustering tools the brain
expression profiles obtained clustered into seven
synexpression groups. The groups were: I,
non-detectable expression (68 ESTs); II, low
expression in hippocampus (40 ESTs); III, low
expression in adult, high expression in newborn (2
ESTs); IV, medium expression throughout brain (31
ESTs); V, high expression throughout brain (3
ESTs); VI, selective high expression in
hippocampus, caudate and putamen (1 EST); VII,
selective high expression in hippocampus (1 EST).
Five ESTs were expressed in the striatum and
responded transcriptionally to neuroleptic and
neuroprotective drug treatments, suggesting that
this approach could be used to detect novel drug
targets. These results provide a useful starting
point to explore the functional genomics of genes
without known functions forthcoming from various
genome projects.
Keywords:
Expressed sequence tags (EST), in situ
hybridization (ISH), gene expression, synexpression
group, striatum (CPu).
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title:
Microarray (Comparative Genomic) analysis of
nonhuman primates: validation of experimental
models in neurological disorders
Markéta Marvanová, Jean
Ménager, and Garry Wong
Non-human
primates (NHPs) have provided robust experimental
animal models for many human related illnesses due
to similar physiologies. Nonetheless, there remain
profound differences in the acquisition,
progression, and outcome of important diseases such
as AIDS and Alzheimer's, for which the underlying
basis remains obscure. We explored the utility of
human high-density oligonucleotide arrays to survey
the transcription profile of NHP genomes. Total RNA
from prefrontal cortices of human (Homo sapiens),
cynomolgus macaque (Macaca fascicularis) and common
marmoset (Callithrix jacchus), was labelled and
hybridized to Affymetrix U95A GeneChip probe
arrays. Corresponding data obtained previously from
chimpanzee (Pan troglodytes) and orangutan (Pongo
pygmaeus) were added for comparison. Qualitative
(present or not detected) and quantitative
(expression level) measures obtained, indicated
that many genes known to be involved in human
neurological disorders were present in NHPs. Two
genes involved in dopamine metabolism (monoamine
oxidase A and catechol-o-methyl transferase) were
absent in both macaque and marmoset suggesting that
some refinement in the use of these animal models
in Parkinson's disease should be addressed.
Transcript profiles of significant numbers of genes
in NHPs provide a comparative genomic basis to
validate experimental animal models while also
indicating the context where these models are most
appropriate.
Keywords: High-density oligonucleotide array, gene
expression, prefrontal cortex (PFC), non-human
primates (NHPs), cynomolgus macaque, and common
marmoset.
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