Accurate and superaccurate gene mapping.

Highly accurate gene mapping techniques need to be developed to clone disease genes with unknown defective products. The classical pedigree method and methods based on cytologically observable chromosome aberrations share definite limits in resolution. We quantify the limits in resolution for the pedigree method. We also discuss a technique for gene localization that exploits the possible presence of minute depletions overlapping the disease locus. One can search for such submicroscopic deletions by aiming random probes at them. We show quantitatively that relatively few probes may suffice to hit a target deletion. Choosing which probes to aim should be guided by pedigree studies and by close examination of relevant cytologically observable translocations and deletions.