AI Article Synopsis
- De novo mutations (DNMs) are significant contributors to severe rare childhood diseases, and early mutations can lead to recurrence through mosaicism in somatic and germ cells.
- A study involving 1,007 sibling pairs identified 878 shared DNMs, estimating recurrence probabilities based on factors like parental mosaicism and mutation types.
- The findings revealed that a majority of shared DNMs (57.2%) were found in parental blood, with paternal mutations showing a decreasing recurrence probability over time compared to maternal mutations, while a new online calculator was developed for estimating these probabilities.
Article 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.
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| http://dx.doi.org/10.1038/s41588-018-0259-9 | DOI Listing |
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