LARGE-SCALE PHYSICAL MAPPING OF HUMAN GENOME .1. GENERATION OF A NOTILINKING LIBRARY

The disadvantages of the NotI libraries available for the human chromo some 3 were analyzed. An improved procedure to generate the NotI libra ries is suggested, allowing one to clone almost all NotI restriction s ites, A representative NotI linking library of the total human genome was generated containing about 20,000 clones. Some genomic DNA fragmen ts flanking the NotI restriction sites were sequenced. The genomic Not I sites were shown to be clustered, with the distance between the neig hboring sites sometimes as small as 24-180 bp.