An optimal algorithm for automatic genotype elimination.

In an effort to accelerate likelihood computations on pedigrees, Lange and Goradia defined a genotype-elimination algorithm that aims to identify those genotypes that need not be considered during the likelihood computation. For pedigrees without loops, they showed that their algorithm was optimal, in the sense that it identified all genotypes that lead to a Mendelian inconsistency. Their algorithm, however, is not optimal for pedigrees with loops, which continue to pose daunting computational challenges. We present here a simple extension of the Lange-Goradia algorithm that we prove is optimal on pedigrees with loops, and we give examples of how our new algorithm can be used to detect genotyping errors. We also introduce a more efficient and faster algorithm for carrying out the fundamental step in the Lange-Goradia algorithm-namely, genotype elimination within a nuclear family. Finally, we improve a common algorithm for computing the likelihood of a pedigree with multiple loops. This algorithm breaks each loop by duplicating a person in that loop and then carrying out a separate likelihood calculation for each vector of possible genotypes of the loop breakers. This algorithm, however, does unnecessary computations when the loop-breaker vector is inconsistent. In this paper we present a new recursive loop breaker-elimination algorithm that solves this problem and illustrate its effectiveness on a pedigree with six loops.