Abstract
Purpose::
To describe lodIRO a freely available web interface for linkage analysis in inherited eye diseases.
Methods::
This interface is composed of a pedigree generator (pedIRO), a data transformer (genIRO) and a linkage calculator (lodIRO). PedIRO is a pedigree drawing program capable of exporting data in a standard file format which can then be uploaded by genIRO together with microsatellite marker values obtained from an ABI sequencer. These files are sorted and assembled to provide chromosome-based linkage output files that can be used by pedIRO to draw pedigrees with haplotypes or by lodIRO to feed various linkage programs (e.g Autoscan, Genehunter, Merlin, Allegro). A linked database containing the most important molecular markers in eye research is used to automatically determine the genetic or the physical distances between markers. These programs run on an OpenMosix clustering solution (comosix.sourceforge.net) that uses the CPU power of idle desktop machines running in the Institute, thus significantly reducing the time needed for calculation. Because all uploaded/downloaded files adhere to common standards, the intermediate results can be shared by any of the freely/commercially available software.
Results::
The mean time normally needed to introduce the marker alleles in a family of 69 persons with 6 consanguineous loops is around 1 week per chromosome and was decreased with the genIRO program to about 2 hours for the whole genome. Helped by lodIRO, the linkage analysis file preparation is also shortened by using the unique interface to the different statistical software. Furthermore, the interpretation of the results is improved by automatically inserting marker distances. As an example, running all statistical tools in parallel on a clustering solution allowed to decrease the typical calculation time for this pedigree by a factor of 30.
Conclusions::
A single web interface reduces the risk of transcription errors from the DNA sequencer through the different programs and facilitates linkage analysis in inherited eye diseases. This facility is freely available to the eye disease research community through the web site www.lodiro.ch.
Keywords: linkage analysis