Somatic and gametic loss of imprinting (LOI) in mammalian development: studies using a novel imprinted transgene on the mouse distal chromosome 7 (MMU7) imprinted region

Genetic inheritance primarily results from the interplay of dominant and recessive genes between two parents. With certain genes, however, gene expression is parent-of-origin-specific: these genes will always be expressed from either the maternal or paternal chromosome. This process is known as genomic imprinting, which creates a mark, or “imprint”, on the chromosome. Gametes are reproductive cells, such as sperm or eggs, which contain a single set of chromosomes. During their maturation, their imprints are erased then re-established. Between the erasure and re-establishment phases is a transitional loss of imprinting (LOI) state. Problems with the erasure or re-establishment of imprints in gametes can result in a number of human genetic disorders, including Prader-Willi, Angelmann, Silever-Russell, and Beckwith-Wiedemann Syndromes. In non-gamete tissues, on the other hand, imprints are generally thought to be maintained throughout life and LOI is often considered to be an abnormal condition. Both loss of epigenetic marks and loss of parent-specific gene expression are observed frequently in many types of cancers, but whether this is a cause or an effect of this abnormal growth is unclear. Meaghan Jones was previously supported by MSFHR for her early PhD studies in genomic imprinting. She is now working to determine more about what causes LOI events in both gametic and non-gametic tissues. She is using a model of Beckwith-Wiedemann Syndrome to determine when LOI occurs in cells, with the hope of pinpointing factors that can cause LOI. An understanding of normal LOI in development could help alleviate the risk of imprinting defects, and could improve effectiveness of medical technologies including assisted reproductive technologies, stem cells, nuclear transfer, and cloning.