A computer-oriented linkage analysis scheme.

Abstract

A comprehensive, computer-oriented scheme for genetic linkage analysis is described. It computes the likelihood of a complex pedigree allowing for many non-standard features including multiple alleles (up to four per locus), multiple mates, more than one mating in the eldest generation, consanguinity, missing or partially tested persons, and different recombination fractions between males and females. The program works by computing weighted likelihoods in a vertical, descending fashion. First, the set of possible genotypes for the members of the eldest generation is determined and prior probabilities assigned to these states of nature (based on gene frequency calculations). Phenotypic information is used to modify these probabilities in the standard manner. Then, for a particular set of genotypes, the conditional likelihood of the remainder of the pedigree is computed. This calculation may itself be many-branched and therefore a computer is necessary to keep track of the stages of the process. When the youngest generation has been taken into account, a final likelihood is determined, reflecting all information in the pedigree. The current version of the program successfully calculates the exact likelihood of a complex pedigree which was designed to exploit the non-standard features of the program. It has also computed likelihoods for a published pedigree, and the results are essentially equal to those obtained by the other authors using a previously available computer scheme for linkage analysis.