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Maximum‐likelihood estimation in linkage heterogeneity models including additional information via the EM algorithm

In linkage analysis, estimated recombination fractions between a disease 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 included in the model. This is demonstrated for 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 of tapetal reflex among obligate female carriers is studied. A model including the additional information is fitted to the data using the EM algorithm. The algorithm uses for every pedigree the lod score curve which can be obtained from a standard (multipoint) linkage analysis. ©1995 Wiley‐Liss, Inc.