De Novo Mutations and Human Disease: the impact of Sex, Age and Selfishness
De novo mutations (DNMs), i.e. genetic alterations not inherited from either parent, are an important contributor to disease, causing severe developmental disorders in ~1 in 300 births. Most DNMs (>80%) originate during spermatogenesis (sperm cell production) and their frequency increases with paternal age. We have previously described a mechanism taking place in the testis of all men that contributes to the paternal age-related increase in pathogenic DNMs called ‘selfish selection’ – whereby specific pathogenic DNMs arising in spermatogonial stem cells lead to their clonal expansion over time. This process explains the paternal age-effect and high birth prevalence observed for several inherited disorders that occur up to 1000-fold more frequently than background. Importantly, because the spermatogonial stem cells provide a source of heritable material, this phenomenon has long-term implications that extend far beyond the individual in whom it takes place, and is predicted to affect disease prevalence, apparent de novo mutation rate and the evolution of our species.
Date: 21 May 2025, 12:30
Venue: John Radcliffe Academic, Headington OX3 9DU
Venue Details: NDCLS Seminar Room, Level 4
Speaker: Professor Anne Goriely (Weatherall Institute of Molecular Medicine, University of Oxford)
Organiser: Dr. Arlene Glasgow (University of Oxford)
Organiser contact email address: arlene.glasgow@ndcls.ox.ac.uk
Host: Prof Deborah Gill (University of Oxford )
Booking required?: Not required
Cost: n/a
Audience: Members of the University only
Editor: Arlene Glasgow