Optimization of Restriction Fragment DNA Mapping

ABSTRACT Consider a mapping project in which overlap of clonal segments is inferred from complete multiple restriction digests. The fragment sizes of the clones are measured with some error, potentially leading to a map with erroneous links. The number of errors in the map depends on the number and types of enzymes used to characterize the clones. The most critical parameter is the decision rule k, or the criterion for declaring clone overlap. Small changes in k may cause an order of magnitude change in the amount of work it takes to build a map of given completion. We observe that the cost of an optimal mapping strategy is approximately proportional to the target size. While this finding is encouraging, considerable effort is nonetheless required: for large-scale sequencing projects with up-front mapping, mapping will be a nonnegligible fraction of the total sequencing cost.