We propose the physical mapping of the human genome from a large genom
ic library through the use of an ordered set of overlapping DNA clones
that span the entire genome. The overlap relations among clones can b
e determined by repeated screening of the library with probes consisti
ng of pooled cloned inserts. The minimum number of probings necessary
for definition of a comprehensive set of overlapping clones can be det
ermined by a simple algorithm. For this approach, most methods are sta
ndard in the technique of "chromosome walking." However, suitable inst
rumentation was required for the repeated and reproducible plating of
highly dense large libraries needed in this approach.