title: New observations on maternal age effect on germline de novo mutations.
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.
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Wendy S W
authors.initials: WS
authors.lastname: Wong
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.|Department of Pediatrics, Virginia Commonwealth University School of Medicine, 1201 E Marshall St, Richmond, Virginia 23298, USA.|Inova Children's Hospital, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Bodian
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Kothiyal
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Eley
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Kathi C
authors.initials: KC
authors.lastname: Huddleston
authors.affiliation: Inova Children's Hospital, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.|Fairfax Neonatal Associates, Inova Health Systems, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Baker
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.
authors.forename: Dzung C
authors.initials: DC
authors.lastname: Thach
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.|Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine, 1201 E Marshall St, Richmond, Virginia 23298, USA.
authors.forename: Ramaswamy K
authors.initials: RK
authors.lastname: Iyer
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.|Department of Pediatrics, Virginia Commonwealth University School of Medicine, 1201 E Marshall St, Richmond, Virginia 23298, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Vockley
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, 3300 Gallows Road, Falls Church, Virginia 22042, USA.|Johns Hopkins University School of Medicine, 733 North Broadway Street, Baltimore, Maryland 21205, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Niederhuber
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D059645:Mutation Rate; D010331:Paternal Age; D055815:Young Adult