6 March 2018

Recently Jakob Goldmann and Christian Gilissen, resp. themes Reconstructive and regenerative medicine and Mitochondrial diseases published an article in Nature genetics.

Publication: Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence.

Clustering of mutations has been observed in cancer genomes as well as for germline de novo mutations (DNMs). We identified 1,796 clustered DNMs (cDNMs) within whole-genome-sequencing data from 1,291 parent–offspring trios to investigate their patterns and infer a mutational mechanism. We found that the number of clusters on the maternal allele was positively correlated with maternal age and that these clusters consisted of more individual mutations with larger intermutational distances than those of paternal clusters. More than 50% of maternal clusters were located on chromosomes 8, 9 and 16, in previously identified regions with accelerated maternal mutation rates. Maternal clusters in these regions showed a distinct mutation signature characterized by C>G transversions. Finally, we found that maternal clusters were associated with processes involving double-strand-breaks (DSBs), such as meiotic gene conversions and de novo deletion events. This result suggested accumulation of DSB-induced mutations throughout oocyte aging as the mechanism underlying the formation of maternal mutation clusters.

Christian Gilissen
Jakob Goldmann

Related news items


Jong KNCV organizes a Pitch competition for PhD candidates

13 August 2020

Are you a PhD candidate and would you like to win 500 euros with a pitch about your research? Young KNCV gives you that chance! During the KNCV Chemistry 2020 Evening on October 8th.

read more

Collective invasion induced by autocrine purinergic loop through connexin-43 hemichannels

13 August 2020

Peter Friedl and Paul Span show in Journal of Cell Biology that breastcancer cells release purines into the extracellular space via connexin-43 hemichannels to control collective invasion.

read more

TP53 allelic state is critical for diagnostic and prognostic precision in blood cancer

12 August 2020

An international study, in which Joop Jansen participated, shows that a double mutaton in TP53 gene deteriotes the prognosis of a rare form of blood cancer. If there is only one mutation or no mutation, then the prognosis is better.

read more

BCG vaccine is safe with no increased risk of COVID-19 symptoms says Mihai Netea

11 August 2020

The BCG vaccine has a general stimulatory effect on the immune system and is therefore effective against multiple infectious diseases - possibly also against COVID-19.

read more

ERC Proof of Concept grant received by Ronald van Rij

30 July 2020

Ronald van Rij, theme Infectious diseases and global health, received an ERC (European Research Council) Proof of Concept grant of 150,000 euros, in order to make arbovirus vaccines even safer.

read more

Hypatia fellowship Call is open

30 July 2020

The Hypatia fellowship round with the deadline 31 May has been canceled. Therefore, the next available deadline will be 27 September 2020. Radboudumc researchers are invited to scout young potentials to fill the strategic gaps within the research themes imbedded in RIHS and RIMLS.  

read more