New observations on maternal age effect on germline de novo mutations

Nature Communications
Wendy S W WongJohn E Niederhuber

Abstract

Germline mutations are the source of evolution and contribute substantially to many health-related processes. Here we use whole-genome deep sequencing data from 693 parents-offspring trios to examine the de novo point mutations (DNMs) in the offspring. Our estimate for the mutation rate per base pair per generation is 1.05 × 10(-8), well within the range of previous studies. We show that maternal age has a small but significant correlation with the total number of DNMs in the offspring after controlling for paternal age (0.51 additional mutations per year, 95% CI: 0.29, 0.73), which was not detectable in the smaller and younger parental cohorts of earlier studies. Furthermore, while the total number of DNMs increases at a constant rate for paternal age, the contribution from the mother increases at an accelerated rate with age.These observations have implications related to the incidence of de novo mutations relating to maternal age.

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Citations

Jun 21, 2016·Nature Genetics·Jakob M GoldmannJohn E Niederhuber
Sep 18, 2016·Evolution, Medicine, and Public Health·Sean G Byars, Jacobus J Boomsma
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Datasets Mentioned

BETA
NA12891
NA12892
ERP001960

Methods Mentioned

BETA
Illumina sequencing
deamination
GAM
Exome Sequencing

Software Mentioned

Tandem repeats finder
BEDTools
Strelka
CGI
RepeatMasker
Illumina Services
Tandem finder
fullyCalledFractionHIGH
GATK
Genome Analysis Toolkit ( GATK )

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