title: Paternal Age Explains a Major Portion of De Novo Germline Mutation Rate Variability in Healthy Individuals.
abstract: De novo mutations (DNM) are an important source of rare variants and are increasingly being linked to the development of many diseases. Recently, the paternal age effect has been the focus of a number of studies that attempt to explain the observation that increasing paternal age increases the risk for a number of diseases. Using disease-free familial quartets we show that there is a strong positive correlation between paternal age and germline DNM in healthy subjects. We also observed that germline CNVs do not follow the same trend, suggesting a different mechanism. Finally, we observed that DNM were not evenly distributed across the genome, which adds support to the existence of DNM hotspots.
authors.affiliation: Département des sciences fondamentales, Université du Québec à Chicoutimi, Saguenay, Canada.|Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Simon L
authors.identifier: http://orcid.org/0000-0002-4089-2280
authors.initials: SL
authors.lastname: Girard
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Cynthia V
authors.initials: CV
authors.lastname: Bourassa
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Quebec, Canada et Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Lemieux Perreault
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Quebec, Canada et Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Legault
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Quebec, Canada et Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Amina
authors.initials: A
authors.lastname: Barhdadi
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Amirthagowri
authors.initials: A
authors.lastname: Ambalavanan
authors.affiliation: Département de Psychologie, Université du Québec à Montréal, Montreal, Canada.
authors.forename: Mara
authors.initials: M
authors.lastname: Brendgen
authors.affiliation: Département de Psychologie de l'éducation, Université de Montréal, Montreal, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Vitaro
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Noreau
authors.affiliation: École de Psychologie, Université Laval, Quebec, Canada.
authors.forename: Ginette
authors.initials: G
authors.lastname: Dionne
authors.affiliation: School of Public Health, University College of Dublin, Dublin, Ireland.|Pediatrics and Psychology, University of Montreal, Montréal, Canada.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Tremblay
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.affiliation: École de Psychologie, Université Laval, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Boivin
authors.affiliation: Centre de Pharmacogénomique Beaulieu-Saucier, Institut de Cardiologie de Montréal, Montreal, Quebec, Canada et Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000328:Adult; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D056915:DNA Copy Number Variations; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010331:Paternal Age; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004247:DNA