Preliminary ordering of multiple linked loci using pairwise linkage data.

Abstract

A method is presented for the preliminary ordering of loci on a chromosome using pairwise linkage data. The method is based on the biologically reasonable assumption that the "true" order of a set of linked loci will be the one that minimizes the total length of the chromosome segment. Here the "length" is defined as the sum of adjacent recombination fractions. The method searches for the optimal order, represented by a minimum distance map (MDMAP), even when it is not possible to examine the n!/2 possible distinct orders for n loci. A computerized approach, using the simulated annealing algorithm of Kirkpatrick et al. [1983], forms the basis of the method. It can be applied to data from radiation hybrid experiments as well as that from conventional family linkage studies. The technique is applied to several sets of published data to illustrate how it performs in practice. The advantages and the disadvantages of the method are discussed so that it will be clear under what conditions it is likely to work well. When data sets are "complete," in the sense that all possible pairwise recombination fractions have estimates, and when no large clusters of extremely tightly linked loci are present, the method produces ordered sets of loci that agree well with those generated by other, more complex methods. Any discrepancies that occur are likely to be with respect to the orientation of nearest-neighbor loci, where relative order cannot be reliably established by any method. The method thus provides a simple, rapid means of obtaining a preliminary order for a set of loci known to be in the same linkage group.