MAXIMUM-LIKELIHOOD-ESTIMATION IN LINKAGE HETEROGENEITY MODELS INCLUDING ADDITIONAL INFORMATION VIA THE EM ALGORITHM

In linkage analysis, estimated recombination fractions between a disea se gene and several markers are used to assign the disease gene to a a particular chromosome region. For rare diseases, locus heterogeneity leads to different recombination fractions in different families, and a set of pedigrees can be regarded as a mixture. Information which can help to classify the different families may be available and can be i ncluded in the model. This is demonstrated far a data set of X-linked retinitis pigmentosa families. The joint distribution of the position of the disease gene and the additional information on the penetrance o f tapetal reflex among obligate female carriers is studied. A model in cluding the additional information is fitted to the data using the EM algorithm. The algorithm uses for every pedigree the lod score curve w hich can be obtained from a standard (multipoint) linkage analysis. (C ) 1995 Wiley-Liss, Inc.