A high number of mutations expanding in the male germline
Sprache des Vortragstitels:
Englisch
Original Tagungtitel:
European Society of Human Genetics
Sprache des Tagungstitel:
Englisch
Original Kurzfassung:
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.
Forschungs-