A PROCEDURE FOR COMBINING 2-POINT LOD SCORES INTO A SUMMARY MULTIPOINT MAP

Multipoint linkage analysis can be extremely demanding in terms of computer time and memory, and these requirements rise exponentially with the number of markers used. A method is described for producing a rapid approximation to a multipoint analysis from the supplied results of two-point analyses with each marker. The method depends on regarding the lod scores as if they were obtained from a number of independent phase-known meioses, and making estimates concerning the proportion of all meioses which are likely to be informative for each marker. It then becomes possible to estimate the amount of information from each marker or pair of markers which is independent of information from other markers. The lod scores arising from independent contributions may then be summed to approximate the true multipoint lod score. The method has been implemented in a computer program called FASTMAP which is freely available. It has been tested on a variety of simulated and real data. In most circumstances it performs well, with a high correlation between the estimated and true multipoint lod score and little bias. However occasionally the results of the estimate deviate markedly from the multipoint lod score, especially at map positions very close to the markers. The overall usefulness of the method will therefore need to be further evaluated, but it does seem adequate at least for building exclusion maps and carrying out preliminary and exploratory analyses.