A strategy for multipoint ordering: example of the 11p markers.

The complete likelihood analysis is required to obtain the evidence for the gene order. Since the number of candidate orders increases rapidly with the number of loci and the complete analysis requires considerable computer time, a method for rapidly screening order is required. To this end, we used the program MAP83 for the initial investigation of order. This method provided a subset of orders to be further investigated by the complete likelihood method. We used PAP for these subsequent analyses. The advantage of algorithms such as MAP83 is that the basic unit of analysis is the set of pairwise LOD scores which are routinely calculated at the beginning of a linkage analysis. However, the magnitude of the log likelihood differences between orders can only be suggestive for two reasons. First, the usual assumptions for MAP83 regarding independence of the recombination fraction estimate are not met by these data and, therefore, no attempt can be made to interpret the log likelihood differences statistically. Secondly, pairwise information precludes identifying the specific inheritance pattern of each gamete, thus the information content of obligatory multiple recombinants is lost. For example, the order HBBC-ADJ-HRAS1-INS requires five double recombinants for the Utah data while the order HBBC-ADJ-INS- HRAS1 does not require any (White et al, 1985). The support for the former order over the latter is a log likelihood difference of 3.73 for the complete likelihood analysis when the HBBC locus is ignored.(ABSTRACT TRUNCATED AT 250 WORDS)