An Unusual High Number of De Novo Mutations in FGFR3 Detected in the Male Germline
Sprache des Vortragstitels:
XXI. Annual Linz Winter Workshop
Sprache des Tagungstitel:
New mutations in the germline are directly transmitted to our children and have profound consequences in future generations. Despite the importance of de novo mutations (DNM) in heritable diseases and evolution, we know very little about the different mutagenic processes in our germline. Of particular interest are a handful of highly recurrent DNM associated with congenital disorders and/or rasopathies, that have been described as driver mutations expanding in the male germline. Most information on germline mutagenesis comes from indirect sequence comparisons or whole genome sequencing of pedigree families, but it renders little information about individual mutagenic events. For this reason, we have adapted an USS technology to study the expansion of selfish genes in the male germilne such as the FGFR3. A pool of sperm DNA from old and another from young donors were used to target a region of the FGFR3 gene using a USS method based on duplex sequencing. We successfully identified numerous high frequency DNM ocurring in the FGFR3 gene in the human male germline. A number of them had been previously described and in some cases they are reported to be related with congenital disorders and/or cancer. We found mutations present in both pools of donors, and those show a higher frequency on older donors.Our USS method has proven to be successful in the detection of high frequency DNM. Also, this method showed to be promising in the detection of potential paternal age effect making this method ideal to discover potential driver DNM that might be expanding with paternal age.