Recent Advances in Imprinting Disorders

Abstract

Genetic imprinting is a biological phenomenon arising from the fact that maternal and paternal contributions to the offspring’s autosomal genes have specific markers or imprints. These imprints contribute uniquely to gene expression based on the parent of origin of the active allele. The discovery of disorders of imprinting is relatively new; in 1989, Prader-Willi syndrome (PWS) was first recognized as an imprinting disorder in humans. It was found that in PWS, despite the presence of normal amount and sequence of DNA material, there is abnormal DNA methylation-induced silencing of the paternal SNRPN gene (on chromosome 15q11q13) that should be normally active in healthy individuals. In such conditions, conventional genetic analyses based on evaluation of DNA sequences may not be diagnostic unless special attention is paid to identifying the parental contributions at specific DNA sites identified as imprinting sites or “differentially methylated regions” in the genome. To date, at least 100 imprinted genes and 12 imprinting disorders have been characterized in humans, and the list is still growing. The use of new and sophisticated molecular techniques for studying genetic and epigenetic phenomena have greatly helped in advancing knowledge in this field. The recognition of various types of epigenetic modifications and their timing of imprint establishment in the human life cycle is providing insights into therapeutic manipulation of the “imprintome” for the prevention and treatment of imprinting disorders. This review summarizes the recent progress made in recognition, diagnosis, and treatment of imprinting disorders.