Avoiding Recomputation in Linkage Analysis

We describe four improvements we have implemented in a version of the genetic linkage analysis programs in the LINKAGE package: subdivision of recombination classes, better handling of loops, better coordination between the optimization and output routines, and a checkpointing facility. The unifying theme for all the improvements is to store a small amount of data to avoid expensive recomputation of known results. The subdivision of recombination classes improves on a method of Lathrop and Lalouel [Am J Hum Genet 1988;42:498-505]. The new method of handling loops extends a proposal of Lange and Elston [Hum Hered 1975;25:95-105] for loopless pedigrees with multiple nuclear families at the earliest generation. From a practical point of view, the most important improvement may be the checkpointing facility which allows the user to carry out linkage computations that are much longer than the mean-time-to-failure of the underlying computer.