Babraham Special EU Studentship: Sequence based prediction and identification of imprinted genes

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

We inherit genes from our fathers and mothers and for most of our genes the copies we receive from either parent are equally active. An important exception to this general rule occurs in a process called genomic imprinting, which results in one copy of some genes being deliberately silenced. These imprinted genes are important in determining how babies grow and how infants adapt their physiology to life outside the womb. Imprinted genes behave in this manner because they are marked in different ways in the male and female germ cells (eggs and sperm). How these marks are made in germ cells and how they are then maintained in the baby and into adult life is not understood, but is important to find out. If the marking process goes wrong problems in fertility or developmental abnormalities may arise; incorrect imprinting is also a cause of cancer and may contribute to other ageing related diseases. Correct imprint marks are also important for the maintenance of stem cells. In this project, we are investigating the signals in our genes that put these marks in place and the processes needed to maintain them throughout life.

Publications

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Description Genomic imprinting is an important epigenetic mechanism in mammals that results in monoallelic silencing of a subset of our genes in a strict parent-of-origin manner. Imprinted genes are particularly important in fetal growth and development, but many also have roles in adult metabolism, energy homeostasis and some brain functions. A number of recent studies have forced us to reassess the general assumption that there are no more than 100-200 genes imprinted genes. This includes our demonstration that there are many more CpG islands differentially methylated in gametes than the known imprinted control regions, as well as transcriptome studies reporting upwards of 1000 transcripts with parental-allele-specific expression in mouse brain. To reconcile these findings, we are mapping parental-allele-specific DNA methylation in mouse embryo tissues, to identify how many gametic methylation differences are retained as parental-allele-specific methylation marks throughout development, and how many candidate imprinted genes predicted by transcriptome studes are associated with gametic methylation marks.
Exploitation Route Imprinted genes may be sensitive epigenetic responders to environmental or nutritional changes. Knowing the full repertoire of imprinted genes will be important widely in appreciating longer-term outcomes of adverse early exposures.
Sectors Healthcare