International Summer School

   From Genome to Life:

    Structural, Functional and Evolutionary approaches

 


 MARVANOVA Marketa

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).

 

 MARVANOVA Marketa

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.