| Literature DB >> 30397338 |
Hákon Jónsson1, Patrick Sulem1, Gudny A Arnadottir1, Gunnar Pálsson1, Hannes P Eggertsson1, Snaedis Kristmundsdottir1, Florian Zink1, Birte Kehr1, Kristjan E Hjorleifsson1, Brynjar Ö Jensson1, Ingileif Jonsdottir1, Sigurdur Einar Marelsson2, Sigurjon Axel Gudjonsson1, Arnaldur Gylfason1, Adalbjorg Jonasdottir1, Aslaug Jonasdottir1, Simon N Stacey1, Olafur Th Magnusson1, Unnur Thorsteinsdottir1,3, Gisli Masson1, Augustine Kong1,4, Bjarni V Halldorsson1,5, Agnar Helgason1,6, Daniel F Gudbjartsson7,8, Kari Stefansson9,10.
Abstract
De novo mutations (DNMs) cause a large proportion of severe rare diseases of childhood. DNMs that occur early may result in mosaicism of both somatic and germ cells. Such early mutations can cause recurrence of disease. We scanned 1,007 sibling pairs from 251 families and identified 878 DNMs shared by siblings (ssDNMs) at 448 genomic sites. We estimated DNM recurrence probability based on parental mosaicism, sharing of DNMs among siblings, parent-of-origin, mutation type and genomic position. We detected 57.2% of ssDNMs in the parental blood. The recurrence probability of a DNM decreases by 2.27% per year for paternal DNMs and 1.78% per year for maternal DNMs. Maternal ssDNMs are more likely to be T>C mutations than paternal ssDNMs, and less likely to be C>T mutations. Depending on the properties of the DNM, the recurrence probability ranges from 0.011% to 28.5%. We have launched an online calculator to allow estimation of DNM recurrence probability for research purposes.Entities:
Mesh：
Year: 2018 PMID： 30397338 DOI： 10.1038/s41588-018-0259-9
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330