Epigene conversion: a proposal with implications for gene mapping in humans. |
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Authors: | J F Sabl and C D Laird |
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Affiliation: | Department of Zoology, University of Washington, Seattle 98195. |
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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. |
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