Of microbes, mice and man

This chapter reviews my 18 years of research in Anne's Unit including studi es on temporal and spatial aspects of X-chromosome inactivation and imprint ing and the role of methylation in X-inactivation in these processes during female mouse embryo development. To enable molecular studies of embryos, w e developed a plethora of single cell assays for specific enzyme activity, gene mutation and methylation, and RNA transcription. While in Anne's Unit, I used these same single cell assays to pioneer the procedures for preimpl antation diagnosis of genetic disease, now an established clinical approach to prevention of the birth of children with severe genetic disease. At the Institute of Child Health in London, we continue to develop new highly sen sitive molecular procedures - currently for the creation of cDNA libraries from human preimplantation embryos, primordial germ cells and embryonal ste m cells, We are using these cDNA preparations to isolate human developmenta l genes and embryo/cancer genes. One of the more fascinating aspects arisin g from my time in Anne's Unit is the way in which my research findings chal lenged a number of accepted dogmas in development concerned with the origin and totipotency of the germ line and the possibility of transgenerational genetic inheritance by epigenetic modification of the germ line.