Abstract
BackgroundComparative genomics is currently one of the most popular approaches to study the regulatory architecture of vertebrate genomes. Fish-mammal genomic comparisons have proved powerful in identifying conserved non-coding elements likely to be distal cis-regulatory modules such as enhancers, silencers or insulators that control the expression of genes involved in the regulation of early development. The scientific community is showing increasing interest in characterizing the function, evolution and language of these sequences. Despite this, there remains little in the way of user-friendly access to a large dataset of such elements in conjunction with the analysis and the visualization tools needed to study them.DescriptionHere we present CONDOR (COnserved Non-coDing Orthologous Regions) available at: . In an interactive and intuitive way the website displays data on > 6800 non-coding elements associated with over 120 early developmental genes and conserved across vertebrates. The database regularly incorporates results of ongoing in vivo zebrafish enhancer assays of the CNEs carried out in-house, which currently number ~100. Included and highlighted within this set are elements derived from duplication events both at the origin of vertebrates and more recently in the teleost lineage, thus providing valuable data for studying the divergence of regulatory roles between paralogs. CONDOR therefore provides a number of tools and facilities to allow scientists to progress in their own studies on the function and evolution of developmental cis-regulation.ConclusionBy providing access to data with an approachable graphics interface, the CONDOR database presents a rich resource for further studies into the regulation and evolution of genes involved in early development.
Highlights
Comparative genomics is currently one of the most popular approaches to study the regulatory architecture of vertebrate genomes
Interrogation and visualization of coding elements (CNEs) by genomic region The central search page allows CNE-containing gene regions to be located from a pull-down list or searched more generally through a text search by gene name, protein accession number, GO term etc for any genes contained within these regions
Each gene region analysed extends as far as the shared synteny and gene order between fish and mammals, allowing for long-range cis-regulatory elements that may lie within or beyond neighbouring genes. These regions are represented in CONDOR View so that users can graphically view the positions of CNEs along a chosen baseline genome in relation to other vertebrate CNEs
Summary
Great advances have been made in our ability to annotate gene sequences, the annotation of sequence elements that control complex gene expression is lagging far behind. With an increasing supply of functional data, we have created CONDOR (Conserved Non-coDing Orthologous Regions), a database resource for the study of evolutionary conserved cis-regulation in early developmental genes Such elements are rigorously defined by optimal alignment strategies for sequences as divergent as fish and tetrapods, ensuring that sequences are derived from orthologous regions. CNEs are searched for further conservation in other available vertebrate genomes that currently include seven mammals, one bird, one amphibian and four teleosts It is clear from a number of recent studies that distal cis-regulatory elements can exert their regulatory influence large distances from their target gene [15], from within the introns of neighbouring genes and across intervening genes [16]. Database populated with external data such as searches against other vertebrate genomes, primer design, RNA secondary structure prediction etc
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