Chromosome jumping is a tool of molecular biology that is used in the physical mapping of genomes. It is related to several other tools used for the same purpose, including chromosome walking.

Chromosome jumping is used to bypass regions difficult to clone, such as those containing repetitive DNA, that cannot be easily mapped by chromosome walking, and is useful in moving along a chromosome rapidly in search of a particular gene. Unlike chromosome walking, chromosome jumping is able to start on one point of the chromosome in order to traverse potential distant point of the same chromosome without cloning the intervening sequences. The ends of a large DNA fragment is the target cloning section of the chromosome jumping while the middle section gets removed by sequences of chemical manipulations prior to the cloning step.

Process

Chromosome jumping enables two ends of a DNA sequence to be cloned without the middle section. Genomic DNA may be partially digested using restriction endonuclease and with the aid of DNA ligase, the fragments are circularized at low concentration. From a known sequence, a primer is designed to sequence across the circularized junction. This primer is used to jump 100 kb-300 kb intervals: a sequence 100 kb away would have come near the known sequence on circularization, it permits jumping and sequencing in an alternative manner. Thus, sequences not reachable by chromosome walking can be sequenced.

NotI-digested DNA

One example to build a library is a classified as a rare-cutting restriction endonuclease such as NotI. In order to construct and characterize a library based from NotI-digested human DNA, random clones were analyzed by restriction mapping. Regardless, it is still deemed to be beneficial due to the possibility to jump over hundred kilobases in comparison to chromosome walking.

Applications

Genetic disorders

Chromosome jumping libraries help address the complication of standard cloning techniques with large molecular distances. This process allowed the possibility to use the chromosome jumping library for other genetic disorders that requires 100 kilobases jumps. Both these complications, traditional cloning techniques are unable to process because large yield of exons would have to be visible to produce a signal for the cystic fibrosis gene to be identified and DNA would have to be free of any repetitive elements.