6 March 2018
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
Recently Jakob Goldmann and Christian Gilissen, resp. themes Reconstructive and regenerative medicine and Mitochondrial diseases published an article in Nature genetics.
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

RIMLS awards call for nominations
19 October 2021 RIMLS awards several prizes to stimulate and honor our (young) researchers. Upcoming awards are Supervisor of the Year, Best Master Thesis, Best Publication, Best Image and more. Send your nominations now before 24 November 2021. read more
Miniaturized microfluidic platform for automated epigenetic profiling
6 May 2021 Together with Fluidigm, a US-based company focusing on microfluidics, the team of Hendrik Marks publishes in Genome Research the development of a powerful plug and play ChIP-seq platform for minute amount of cells, such as embryonic specimens or small biopsies. read more

RIMLS online award ceremony proudly presenting the winners
13 January 2021In this special webinar of the RIMLS New Year Celebration, scientific director René Bindels reviewed 2020 and looked forward to 2021. But more importantly a number of researchers received prizes in the traditional RIMLS awards ceremony.
read more
RIMLS PhD retreat registration is open
23 January 2020 Yearly, RIMLS PhD candidates gather for the two-day PhD Retreat. Apart from the science, this event is highly valued for the opportunity to meet and get to know fellow PhD candidates during the social activities. Early bird registration and abstract submission deadline: 4 March 2020. read more
RIMLS awards call for nominations
26 November 2019 RIMLS awards several prizes to stimulate and honor our (young) researchers. Please find here an overview of the upcoming awards. Deadline 12 December 2019. read more