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


Radboud-led collaboration generates innovative candidate drug against malaria

19 September 2019

A molecule once designed to cure the skin disease psoriasis appears to be particularly effective against malaria. The antimalarial properties were revealed thanks to one researcher’s inspired hunch when the psoriasis drug discovery programme came to a dead end.

read more

Radboud university medical center opens first healthcare AI labs

19 September 2019

These are the first two ‘labs’ in the east of the Netherlands that are part of the national Innovation Center for Artificial Intelligence and the first health labs. With these two initiatives, Radboudumc and its partners are investing heavily in the application of AI to health care.

read more

A personal touch of Kartika Hapsari

18 September 2019

In order to promote interaction amongst colleagues within RIMLS, we have a ‘personal touch’ series setting employees in the spotlight. A light-hearted manner to learn about the colleagues you know and those you don’t. This week: Kartika Hapsari.

read more

How team science can make a difference!

17 September 2019

All researchers and others involved in the Healthy Brain Study on the Radboud Campus are invited for the next Progress Meeting that takes place on Wednesday, 2 October 2019.

read more

MMD Lecturer of the year award for Alessandra Cambi

16 September 2019

At their annual MMD symposium, Alessandra Cambi, theme Nanomedicine, was chosen as lecturer of the year 2018-2019 of the Top Master "Molecular mechanisms of disease". 

read more

Artificial intelligence for renal tissue assessment

16 September 2019

Meyke Hermsen and Jeroen van der Laak, present an alternative approach, featuring a convolutional neural network for multi-class segmentation of periodic acid–Schiff-stained kidney tissue sections. Their work was published in the Journal of the American Society of Nephrology.

read more