Objective
For the understanding of the basic DNA-structure, and thus its organisation and regulation, sequence comparisons between different species are a prerequisite. Studies of this kind provide information on the distribution, frequency and variation of DNA-features and form the basis for experiments on their relevance to functions. Knowledge of the ubiquity (or rarity) and similarity of particular, regulative DNA-structures, for instance, could permit a directed influence on a certain group of cell-functions.
As a pilot project aimed at the refinement of the relevant procedures, so that eventually large DNA-segments or even entire chromosomes or genomes can be examined, a genomic region known to be homologous in the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, mouse and human will be studied. The genomic regions around the conserved homologues of the Drosophila melanogaster flightless-(fliI) gene in the above organisms will be used initially. The human region is of particular interest, since three distinct inherited chromosomal anomalies map to this chromosomal area. Genomic clones and cDNAs of the fliI homologues will be hybridised with short oligomer sequences, that is hexamer to decamer oligonucleotides, whereby a partial sequence of the studied DNA fragments is obtained.
Complementary experiments will be carried out with either the oligomers or the DNA fragments presented on a support matrix in the form of an ordered array. Already with randomly chosen oligomers, comparisons can be made based on a statistical analysis of frequency, combination and intensity of oligomer binding. Using also selected oligonucleotides resembling sequence motifs, data obtained from such experiments directly provide information on the DNA structure, such as the position and kind of repeats or regulatory elements. Thus, the DNA segments will not only be compared but simultaneously they can be assessed on the basis of this partial sequence information before any further work-intensive and costly complete sequence analyses are carried out. In addition to the fliI locus, further DNA regions, such as variable regions of mitochondria or the p53 gene, will be worked on at later stages of the project.
Topic(s)
Call for proposal
Data not availableFunding Scheme
Data not availableCoordinator
69120 Heidelberg
Germany