“De novo mutations and human disease: the role of sex, age and selfishness”
Abstract – 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 de novo mutations (DNMs) are an important contributor to human disease, causing developmental disorders in >1:300 births. While it is widely thought that DNMs occur randomly as DNA copy-errors during spermatogenesis, we have challenged this assumption by showing that so-called ‘selfish’ mutations are able to hijack spermatogonial stem cell homeostasis, 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 DNMs 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 contributes to genome heterogeneity and to the mutational burden associated with complex disorders.

Bio: After an undergraduate degree in Engineering (Agronomy) at the Université Libre de Bruxelles (Belgium), Anne Goriely obtained a PhD studying the development of the nervous system of the Drosophila embryo. She spent 4 years in New York at Cornell Medical School and Rockefeller University, before moving to the UK to work on the nervous system development of the chick embryo. In 2000 she joined the MRC Weatherall Institute of Molecular Medicine (University of Oxford) to study the origin of rare human developmental disorders associated with paternal age effects.

She is currently Professor of Human Genetics based at the MRC Weatherall Institute of Molecular Medicine in Oxford. Using a human genetics approach, her group’s main interests lie in elucidating the mechanisms by which we acquire new germline mutations and the implications of such processes in health and disease.

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As a reminder, the (gen)omics seminar series runs every other Thursday morning and is intended to increase interaction between individuals working in genomics across Oxford. We encourage in-person attendance where possible. There is time for discussion over tea, coffee and pastries after the talks.

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Please note, these meetings are closed meetings and only open to members of the University of Oxford to encourage sharing of new and unpublished data. Please respect our speakers and do not share the link with anyone outside of the university. The aim of these seminars is to increase interaction between people working in Genomics across the University so we encourage in person attendance wherever possible.

Microsoft Teams meeting
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Meeting ID: 363 436 205 129
Passcode: e4fp8a
Date: 16 November 2023, 9:30 (Thursday, 6th week, Michaelmas 2023)
Venue: Big Data Institute, Old Road Campus OX3 7LF
Venue Details: Seminar Room 0
Speaker: Professor Anne Goriely (Weatherall Institute of Molecular Medicine, University of Oxford)
Organising department: Big Data Institute (NDPH)
Organisers: Sumeeta Maheshwari (University of Oxford), Nicola Whiffin (University of Oxford), Duncan Palmer (University of Oxford)
Organiser contact email address: sumeeta.maheshwari@ndph.ox.ac.uk
Part of: BDI/CHG Genomics Seminar Series
Booking required?: Not required
Cost: free
Audience: Members of the University only
Editor: Sumeeta Maheshwari