title: Epigene conversion: a proposal with implications for gene mapping in humans.
abstract: Epigenetic modification of DNA is now recognized as a potentially important factor in the inheritance and expression of some mutations; its ability to complicate human genetic analysis is concurrently becoming apparent. One unusual form of epigenetic modification, dominant position-effect variegation (PEV), has been used as a model for Huntington disease. In dominant PEV, a fully dominant mutant phenotype results from stable epigenetic inactivation of an allele adjacent to the structural alteration (cis-inactivation) combined with a complementary inactivation of the homologous normal allele (trans-inactivation). We now propose that trans-inactivation of the normal allele may occasionally persist through meiosis. Such "epigene conversion" occurring at the Huntington disease locus in a few percent of meioses would largely account for the published anomalies in that region's genetic map. This concept could also explain anomalous linkage map data for other disease-causing alleles in humans.
authors.affiliation: Department of Zoology, University of Washington, Seattle 98195.
authors.forename: J F
authors.initials: JF
authors.lastname: Sabl
authors.forename: C D
authors.initials: CD
authors.lastname: Laird
mesh_terms: D002874:Chromosome Mapping; D003434:Crossing Over, Genetic; D004247:DNA / Q000235:genetics; D005785:Gene Conversion; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D008540:Meiosis; D008957:Models, Genetic; D011995:Recombination, Genetic
chemical_list: D004247:DNA