A high number of mutations expanding in the male germline

Description

Background/Objectives: The higher risk of older fathers having an affected offspring with early or late-onset rare disorders has been quite unsettling; but unfortunately, the methods have been limited to better characterize this phenomenon. So far, studies have focused on well-characterized mutations mainly identified in the receptor tyrosine kinase receptor (RTK) signalling pathway [1-3]. Methods: The establishment of duplex sequencing opened exciting new possibilities in ultra-rare variant detection with a very high accuracy for a sequencing-based method [4, 5]. This is the first study that has used this sequencing approach to explore this type of mutagenesis directly in sperm in the FGFR3 gene. Results: We found mutations associated with congenital disorders at increased frequencies and identified new unreported selfish mutations expanding with age [6]. We further characterized the expansion of these in the male germline with droplet digital PCR and analysed the change in receptor signalling [7, 8]. Conclusion: Our work sheds light into different mutational mechanisms potentially affecting the receptor kinase activity.

Period	11 Jun 2022
Event title	European Society of Human Genetics
Event type	Conference
Location	AustriaShow on map