title: Maximum-likelihood estimation in linkage heterogeneity models including additional information via the EM algorithm.
abstract: In linkage analysis, estimated recombination fractions between a disease gene and several markers are used to assign the disease gene to 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.
authors.affiliation: Department of Medical Statistics, Leiden University, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: L A
authors.initials: LA
authors.lastname: Sandkuijl
authors.forename: A A
authors.initials: AA
authors.lastname: Bergen
authors.forename: H C
authors.initials: HC
authors.lastname: van Houwelingen
mesh_terms: D000465:Algorithms; D005260:Female; D018740:Genetic Heterogeneity; D006579:Heterozygote; D006801:Humans; D016013:Likelihood Functions; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D011995:Recombination, Genetic / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*