TY - JOUR
T1 - New observations on maternal age effect on germline de novo mutations
AU - Wong, Wendy S.W.
AU - Solomon, Benjamin D.
AU - Bodian, Dale L.
AU - Kothiyal, Prachi
AU - Eley, Greg
AU - Huddleston, Kathi C.
AU - Baker, Robin
AU - Thach, Dzung C.
AU - Iyer, Ramaswamy K.
AU - Vockley, Joseph G.
AU - Niederhuber, John E.
N1 - Funding Information:
We thank the ITMI clinical, laboratory, IT and informatics staff for their support on this research project, and would like to express our gratitude to all participants in the studies. This work was supported by the Inova Health System, a non-profit healthcare system in Northern Virginia.
PY - 2016/1/19
Y1 - 2016/1/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84955601029&partnerID=8YFLogxK
U2 - 10.1038/ncomms10486
DO - 10.1038/ncomms10486
M3 - Article
C2 - 26781218
AN - SCOPUS:84955601029
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 10486
ER -