Sex-linked dosage-sensitive modifiers as imprinting genes.
It is proposed that differential genome imprinting is the result of dosage-sensitive modifier genes located on the sex chromosomes. Parallels between variegating position-effects in Drosophila, the phenotype elicited by transgenes in the mouse and data from several pediatric tumors indicate that the net result of the activity of such modifier genes is often cellular mosaicism in the expression of affected alleles. The mechanism by which inactivation of affected alleles is achieved is proposed to be through the formation of heterochromatic domains. Because the relevant sex-linked modifying loci are dosage sensitive in their activity, differential imprinting will occur even within homogeneous genetic backgrounds. The presence of allelic variants at these loci in non-inbred populations will give rise to variation in the observed expressivity and mode of inheritance of affected traits.
Sapienza
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Ludwig Institute for Cancer Research, Montreal, Quebec, Canada.
D000818:Animals; D004303:Dosage Compensation, Genetic; D004330:Drosophila; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics; D008957:Models, Genetic; D010641:Phenotype; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012730:Sex Chromosomes / Q000502:physiology*