The rapid rise in complex diseases (e.g. infertility, diabetes, cancer and autism) indicate that the most prevalent human illnesses are not due to genetics alone. Rather the inheritance of disease risk is from a combination of gene-environment interactions in the sperm and egg. This phenomenon is known as epigenetic inheritance.
Discovering how environmental memories are transmitted across generations has been elusive and controversial. It is essential to define the molecular mechanisms underlying epigenetic inheritance to develop pharmaceutical tools and health interventions to prevent the transmission of disease by epigenetic inheritance. Scientists agree that the biological candidates implicated in epigenetic inheritance include DNA methylation, the histones and non-protein coding RNA. The studies that identified these three epigenetic factors were conducted primarily in rodent models. Whether they act in a similar manner in humans is unknown.
In 2023 the full human reference genome became available unveiling previously dark regions of the genome that are likely to be involved in epigenetic inheritance. This advance sets the stage for investigation of the root causes of epigenetic disease inheritance.
Our team of international experts will delineate how environmental exposure information is encoded in the sperm to alter health across generations. To do so, we will probe the sperm epigenome from two generations of men that took part in unique in the world longitudinal studies comprised of fathers and sons from Finland and Denmark. In parallel, we will use a rodent model of transgenerational epigenetic inheritance to validate our findings from the human cohorts. This research will be transformational as it may uncover new routes to human disease. Unlike disease that is cause by variants in the DNA, epigenetic causes of disease open the door for novel therapeutics and preventative strategies as the epigenetic layer is dynamic and can be modified.
