RELATIONAL GENOME ANALYSIS USING REFERENCE LIBRARIES AND HYBRIDIZATION FINGERPRINTING

The genomes of eukaryotic organisms are studied by an integrated appro ach based on hybridisation techniques. For this purpose, a reference l ibrary system has been set up, with a wide range of clone libraries ma de accessible to probe hybridisation as high density filter grids. Man y different library types made from a variety of organisms can thus be analysed in a highly parallel process; hence, the amount of work per individual clone is minimised. In addition, information produced on on e analysis level instantly assists in the characterisation process on another level. Genetic, physical and transcriptional mapping informati on and partial sequencing data are obtained for the individual library clones and are cross-referenced toward a comprehensive molecular unde rstanding of genome structure and organisation, of encoded functions a nd their regulation. The order of genomic clones is established by hyb ridisation fingerprinting procedures. On these physical maps, the loca tion of transcripts is determined. Complementary, partial sequence inf ormation is produced from corresponding cDNAs by hybridising short oli gonucleotides, which will lead to the identification of regions of seq uence conservation and the constitution of a gene inventory. The hybri disation analysis of the cDNA clones, and the genomic clones as well, could potentially be expanded toward a determination of (nearly) the c omplete sequence. The accumulated data set will provide the means to d irect large-scale sequencing of the DNA, or might even make the sequen ce analysis of large genomic regions a redundant undertaking due to th e already collected information.