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Physical Maps Using Chromosome Walking and Jumping OR Hopping - The techniques of chromosome walking and jumping were earlier described. The centromeric sequences on a yeast chromosome could be isolated using chromosome walk from two cloned genes CDC10 and LEU 2 on either side of the centromere.

Walks have also been used to establish the structure of some very large Drosophila genes that are much too long to be cloned even in cosmids. Unfortunately chromosome walks are difficult in higher eukaryotes, due to the presence of repetitive sequences flanking majority of the genes, which allow cross hybridization.

Therefore, the fragments of DNA can not be arranged along the length of chromosomes in higher eukaryotes. Chromosome jumping technique has been used to cross large distances to approach closer to a gene of interest.

Size selected DNA fragments are generated by partial MboI digestion and a jumping library is prepared. Jumping has the additional advantage of allowing one to jump over otherwise unclonable sequences.

In humans, following jumping libraries, besides others, have been prepared.

(1) 100 kb jumping library to move towards Cystic Fibrosis (CF) locus

(2) 200 kb jumping library to move toward Huntington Disease (HD)

In these cases clones are, derived which jump from a given locus (probe) towards the gene of interest. The jumping library (with 2 x 106 clones) is screened using closely linked probes that were labeled.

Positive phage clones are subcloned and used for further chromosome jumping.The gene responsible for Huntingtion Disease (HD*) in humans, is one such gene that is identified through its close linkage to the DNA marker DHS10, which, by in situ hybridization and somatic cell genetics, has been mapped near the tip of the short arm of chromosome 4 (4p).

Chromosome jumping was used to move from DHS10 to HD. Similarly cystic filorosis gene was also mapped using chromosome jumping.