The traditional view has been that the DNA sequence of an individual's genome carries all heritable information. In mammals, the DNA and the proteins carrying the DNA undergo chemical, so called epigenetic modifications that do not affect the DNA sequence. It is now known that some epigenetic modifications are passed on to the next generation.
Mammalian offspring receive two copies of each gene, one inherited from the mother, the other from the father. Typically, the two copies are equivalent, that is, either they are both active (produce RNA transcripts that are translated into proteins) or inactive. However, for a small number of genes, the parental origin of a gene copy determines its activity. These genes are known as imprinted genes because one of the two copies carries an epigenetic mark that was established in either the egg or the sperm. The cell's machinery uses this mark to distinguish the maternal from the paternal copy and to specifically silence one of them. While there are relatively few imprinted genes, they are crucial for normal growth and development, both before and after birth. Genetic or epigenetic disruption of imprinted genes often results in the individual's early demise or leads to disease. In humans, for example, various birth defects and cancers have been associated with imprinted genes. My work as an EMBO fellow focused on the identification of novel imprinted genes in the mouse. The mouse is a good model organism in which to study imprinting. Most murine imprinted genes are also imprinted in humans, and vice versa. Mouse genetics is well understood and has been used to breed mice with chromosomal abnormalities that combined with the DNA chip technology are powerful tools for imprinted gene discovery. Using this approach, our group has identified ten novel imprinted genes in the mouse.
