Intergenomics on QTLsTopic
Quantitative trait loci (QTL) mapping efforts have been performed independently for several species for the same traits. If the animal models are driven by the same genetic mechanisms as those for the human diseases, we should expect to find common conserved sequences shared by the QTLs and susceptibility regions of all three organisms. Genes present as homologues in the QTLs of all three species, arise as best candidates to be relevant for the onset and/or further development of the disease.
A comprehensive QTL database for rodent EAE was created with data collected from the public databases of the NCBI, the Jackson Laboratory (MGI: Mouse Genomics Informatics) and the Rat Genome Database (RGD) of the Medical College of Wisconsin. The data were complemented with human MS predisposition loci and genes assembled both from public databases of the NCBI and recent large scale genetic linkage studies on MS (mainly: J Neuroimmnol vol 143/1-2).
Consensuses may occur by chance with a certain probability. In order to determine that probability, here we test the performance of the intergenomics QTL synteny tool on randomly located QTLs of the same size as the original ones (Monte Carlo simulation). With an increasing number of iterations, the calculated distribution fits the real random distribution. That distribution yields the probability of finding by chance a certain number of genes in consensuses. Whenever the observed number of genes in consensuses is above the 95th percentile limit, it can be concluded that the observed number is reached or surpassed only five from hundred cases (i.e. p<0.05).
WARNING: Depending on the number and the size of the loci added to the system, the consensus search may take several hours to complete. However, the browser allows mostly to follow the process as it goes on (does not apply to some versions of Konqueror).
There are two ways implemented for setting the limits of a QTL / susceptibility locus. The first one fixes those borders on the corresponding centroid value (default). That value corresponds to the most probable physical position of the given genetic marker as calculated from the genetic position by CARTOGRAPHER (Voigt et al. 2004 Non-linear conversion between genetic and physical chromosomal distances. Bioinformatics, in press). The conversion was made with an outlier tolerance of 20% and a scrolling window size of 20 points. For those markers not listed in base pair position or, instead, the physical position when available in EnsEMBL. The second way is to extend the borders to the external confidence interval as provided by CARTOGRAPHER.
This checkbox allows to switch between the full table display (see OUTPUT) and the compact display showing only the final results (quicker).
The output is formatted as a large HTML table. The left column series (yellow) displays the chromosomal regions analyzed for the source species. The middle part (light orange) - if present - shows the chromosomal regions inside of QTLs of the intermediate species that are syntenic to the ones of the left column series (yellow). The right column series displays the chromosomal regions syntenic to the foregoing consensus regions between source and intermediate species (in case of three-way analysis) or syntenic to the source species (in case of two-way analysis) outside (dark orange) or inside (red) of the QTLs or susceptibility loci of the target species. The loci displayed all link to the EnsEMBL contigview in order to assist in further analyses.
AvailabilityCurrent scripts and databases used by QTL VIEW include:
QTLVIEW randomizer: a less user friendly - but considerably quicker - version of the foregoing script running on the same QTLs and susceptibility loci, but randomized in position over the genome (requires PHP4)
QTLVIEW randomizer batch to automatize the foregoing script (C-SHELL script; requires Unix/Linux)
QTLVIEW random distribution analyzer to calculate the quantiles (requires PERL)
DATABASE on EAE QTLs and MS susceptibility loci (as CSV file; requires an SQL-based database system)
ENSEMBL DATABASES on the human, mouse and rat genome and their syntenic relationship
The scripts and database available here are Open Source. This means they are license-free in use and distribution. However, the authorship should be indicated whenever the scripts/database are publicly used. The links and paths to the database in the PHP scripts and between the PHP scripts refer strictly to our local network architecture and should therefore be readjusted after a local installation (!). Developers are encouraged to feed back corrections and improvements, and any user is of course welcome to collaborate in debugging the software.
AuthorsQTL View was created by Pablo Serrano-Fernández, Steffen Möller, Saleh M. Ibrahim, Hans-Jürgen Thiesen (Immunology, University of Rostock), Uwe K. Zettl (Neurology, University of Rostock), René Gödde and Jörg T. Epplen (Human Genetics, University of Bochum).
For technical help, comments or questions please contact Pablo Serrano-Fernández or Steffen Möller.
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