Speaker: Anne Goriely, Ph.D.
Title: “Ageing men, their selfish testes, new mutations and human disease”
Because mutations are at the origin of all genetic variations, understanding the factors that influence the rate at which they occur in our genome is crucial to the study of evolution and disease. Over the last decade, thanks to the systematic implementation of Next-Generation Sequencing, it has become apparent that new mutations are an important contributor to human disease, causing developmental disorders in >1:300 births. While it is widely thought that new mutations occur randomly as DNA copy-errors during spermatogenesis, we have challenged this assumption by showing that so-called ‘selfish’ mutations are able to hijack the way sperm production is controlled to their own advantage, leading to their preferential transmission to the next-generation – where they cause severe disorders associated with strong paternal age effects.
In this presentation I will summarise our current understanding of de novo mutations in humans, the impact of advanced paternal age and their importance for human disease. I will then describe the findings that have led to the discovery of the ‘selfish selection’ process in human testes and propose that this mechanism may contribute to the mutational burden associated with complex disorders, including neurocognitive disorders such as autism and schizophrenia.