Department of Pathology, College of Physicians and Surgeons; Columbia University
It is now 7 years since the identification of imprinted genes in mice. Since then, systematic efforts in many laboratories, including ours, have paid off in the identification and characterization of a substantial number of additional bona fide imprinted genes in the mouse and human genomes. This information can now be used to begin to test theories of the mechanism and biological rationale of imprinting. It is also now possible to address the issue of the existence and extent of interindividual variation in the strength of imprinting and the effect of both genetic and environmental influences on the primary imprint and its maintenance in somatic cells. These are important questions, not least because aberrant DNA methylation and pathological silencing or activation of specific imprinted genes is strongly implicated as an early and permissive mechanism in multistage tumorigenesis. Data from multipoint epigenetic analysis within the megabase-scale imprinted domain on human chromosome 11p5.5 and its counterpart on mouse chromosome 7 will be discussed in the context of these questions.