We have long appreciated that children born carry unique genomes that are a mixture of their parents DNA. The diversity in our genomes is the result of the introduction of damage to DNA in the germ cells (sperm and eggs) and this creates a paradox. DNA damage is typically associated with genome instability: rearranged and mutated genomes associated with ageing, cancer and neurodegenerative disorders. However, in germ cells such as eggs and sperm the programmed introduction of DNA damage and its repair is essential to generate diversity in children.
In this programme (ReCAP), we have begun to study how the generation of diversity is balanced with genome stability, directly in human eggs and preimplantation embryos. This is because 20% of human eggs carry an extra or missing chromosome are thus highly unstable. Upon fertilization by sperm, this results in an unbalanced genome that is not able to sustain embryo and fetal development in the vast majority cases. This results in both preclinical and clinical pregnancy loss. In the rare live births, extra chromosomes can, but does not have to, result in congenital disorders.
Our overall objectives are to understand how genome diversification and DNA damage impact on reproductive health in women and the genetic health in children. We thereby aim to provide the underlying science on which health policies can be based and that may provide improved insight and social impact into pregnancy loss and infertility.
