Statistical analysis of DNA fingerprint data for ordered clone physical mapping of human chromosomes

A statistical framework is proposed for analysing DNA fingerprint data from experiments aimed at constructing ordered clone physical maps of chromosomes. The fingerprint data consists of the lengths and hybridization states of restriction digest fragments and the paper develops a solution to the fundamental problem of deciding whether or not two randomly selected clones overlap. Overlap probabilities are calculated using Bayes' rule together with appropriate statistical descriptions of the chromosome and experimental procedure. The analysis is flexible, allowing a variety of assumptions to account for experimental errors and difficulties, such as unobserved fragments. The approach described here provides a basis for predicting the rate of progress of an experimental protocol and hence for comparing alternate protocols. It is readily generalized to related problems with a wide range of possible data. Results are presented for the clone mapping protocol currently being employed at Los Alamos National Laboratory on human chromosome 16 (Stallings et al., 1990, Proc. natl. Acad. Sci. U.S.A., 87, 6218-6222).