Page 30 - PCC08

Selfish de novo mutations and advanced paternal age: implications for human disease
Anne Goriely
Anne.Goriely@imm.ox.ac.uk
MRC Weatherall Institute of Molecular Medicine University of Oxford, UK
(Declaration: no conflict of interest)
Main learning points covered in this lecture:
De novo mutations – ‘rare’ but globally important contributor to disease
The mutable genome of multicellular organisms  germline vs. somatic mutations
Measuring the human mutation rate via WGS trio (father-mother-child) sequencing
- spermatogenesis:pointmutationsincreasewithpaternalage
- Oogenesis:chromosomalaneuploidyriskincreaseswithmaternalage
The study of rare human disorders can reveal important biological processes Paternal-age effect is associated with ‘selfish selection’
Selfish mosaicism is a universal process: although germline is resilient to mutation accumulation, some pathogenic mutations can hijack spermatogonial stem cells  importance in evolution/disease
Page 24 of 102
30