Genomic Imprinting and Its Effects on Genes and Chromosomes in Mammals

Genomic imprinting is a regulatory mechanism by which, at certain gene loci, one of the two alleles becomes repressed according to its parental origin. This chapter focuses on mammalian imprinting, which regulates not only the parental allele-specific gene expression on autosomal chromosomes: in the extra-embryonic tissues of female mouse embryos, it also determines the choice of the X chromosome to be inactivated. In this chapter, we introduce autosomal and the X chromosome imprinting in mammals and summarize the current understanding of its underlying mechanisms. Presented are examples of deregulation of imprinted genes in animal models and in human disease that arise as a consequence of deletion or acquisition of parental chromosomes. The chapter discusses the possible impact of imprinting on transgenes and artificial chromosomes and describes that in vitro manipulation and culture of cells and embryos may disrupt imprinting and can thereby lead to aberrant phenotype. The latter could be relevant relative to the application of transgenic and chromosome methodologies. Most of the presented examples in the chapter relate to experimental work on mouse models. Because imprinting is highly conserved among placental mammals, however, emerging ideas and concepts are valid for human and ruminant model systems as well.