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Biologically meaningful expression profiling across species using heterologous hybridization to a cDNA microarray.

ABSTRACT: BACKGROUND: Unravelling the path from genotype to phenotype, as it is influenced by an organism's environment, is one of the central goals in biology. Gene expression profiling by means of microarrays has become very prominent in this endeavour, although resources exist only for relatively few model systems. As genomics has matured into a comparative research program, expression profiling now also provides a powerful tool for non-traditional model systems to elucidate the molecular basis of complex traits. RESULTS: Here we present a microarray constructed with approximately 4500 features, derived from a brain-specific cDNA library for the African cichlid fish Astatotilapia burtoni (Perciformes). Heterologous hybridization, targeting RNA to an array constructed for a different species, is used for eight different fish species. We quantified the concordance in gene expression profiles across these species (number of genes and fold-changes). Although most robust when target RNA is derived from closely related species (<10 MA divergence time), our results showed consistent profiles for other closely related taxa (approximately 65 MA divergence time) and, to a lesser extent, even very distantly related species (>200 MA divergence time). CONCLUSION: This strategy overcomes some of the restrictions imposed on model systems that are of importance for evolutionary and ecological studies, but for which only limited sequence information is available. Our work validates the use of expression profiling for functional genomics within a comparative framework and provides a foundation for the molecular and cellular analysis of complex traits in a wide range of organisms.

SUBMITTER: Renn SC

PROVIDER: S-EPMC471549 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature

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Biologically meaningful expression profiling across species using heterologous hybridization to a cDNA microarray.

Renn Susan C P SC Aubin-Horth Nadia N Hofmann Hans A HA

BMC genomics 20040706 1

<h4>Background</h4>Unravelling the path from genotype to phenotype, as it is influenced by an organism's environment, is one of the central goals in biology. Gene expression profiling by means of microarrays has become very prominent in this endeavour, although resources exist only for relatively few model systems. As genomics has matured into a comparative research program, expression profiling now also provides a powerful tool for non-traditional model systems to elucidate the molecular basis ...[more]

PMID: 15238158

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Project description:BackgroundHuman endogenous retroviruses (HERVs) have received much attention for their implications in the etiology of many human diseases and their profound effect on evolution. Notably, recent studies have highlighted associations between HERVs expression and cancers (Yu et al., Int J Mol Med 32, 2013), autoimmunity (Balada et al., Int Rev Immunol 29:351-370, 2010) and neurological (Christensen, J Neuroimmune Pharmacol 5:326-335, 2010) conditions. Their repetitive nature makes their study particularly challenging, where expression studies have largely focused on individual loci (De Parseval et al., J Virol 77:10414-10422, 2003) or general trends within families (Forsman et al., J Virol Methods 129:16-30, 2005; Seifarth et al., J Virol 79:341-352, 2005; Pichon et al., Nucleic Acids Res 34:e46, 2006).MethodsTo refine our understanding of HERVs activity, we introduce here a new microarray, HERV-V3. This work was made possible by the careful detection and annotation of genomic HERV/MaLR sequences as well as the development of a new hybridization model, allowing the optimization of probe performances and the control of cross-reactions. RESULTS: HERV-V3 offers an almost complete coverage of HERVs and their ancestors (mammalian apparent LTR-retrotransposons, MaLRs) at the locus level along with four other repertoires (active LINE-1 elements, lncRNA, a selection of 1559 human genes and common infectious viruses). We demonstrate that HERV-V3 analytical performances are comparable with commercial Affymetrix arrays, and that for a selection of tissue/pathological specific loci, the patterns of expression measured on HERV-V3 is consistent with those reported in the literature.ConclusionsGiven its large HERVs/MaLRs coverage and additional repertoires, HERV-V3 opens the door to multiple applications such as enhancers and alternative promoters identification, biomarkers identification as well as the characterization of genes and HERVs/MaLRs modulation caused by viral infection.

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Biologically meaningful expression profiling across species using heterologous hybridization to a cDNA microarray.

Publications

Biologically meaningful expression profiling across species using heterologous hybridization to a cDNA microarray.

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