Replicon map of the human dystrophin gene: asymmetric replicons and putative replication barriers

摘要

Using the replication direction assay and oligonucleotide probes designed on the basis of the known exon sequences of the human dystrophin gene we have made a replicon map of this giant gene. It has been found that dystrophin gene is organized into at least six replicons ranging in size from 170 to more than 500 kb. One of the replicon junctions (sites of replication termination) was mapped in intron 44, i.e. roughly in the same area where the major recombination hot spot is located. It is also worth mentioning that the central part of the dystrophin gene (exons 8 - 48) is organized into relatively short symmetrical replicons surrounded by two extended regions of apparently unidirectional replication (exons 1 - 8 and exons 49 - 64). These observations suggest for the first time that there should be certain signals for the termination of replication in euchromatic areas of the genome of higher eukaryotes. Furthermore, it may be concluded that the replication of the central part of dystrophin gene must be completed much faster than the replication of its ends. This may induce some topological stresses resulting in an increased rate of chromosomal rearrangements within this gene. The experimental approach used in our study may be helpful for fast analysis of the replication structure of other areas of the human genome provided that these areas are saturated with STS markers.