Paternal Age Explains a Major Portion of De Novo Germline Mutation Rate Variability in Healthy Individuals

• Published in: PloS one Vol. 11; no. 10; p. e0164212
• Main Authors: Girard, Simon L., Bourassa, Cynthia V., Lemieux Perreault, Louis-Philippe, Legault, Marc-André, Barhdadi, Amina, Ambalavanan, Amirthagowri, Brendgen, Mara, Vitaro, Frank, Noreau, Anne, Dionne, Ginette, Tremblay, Richard E., Dion, Patrick A., Boivin, Michel, Dubé, Marie-Pierre, Rouleau, Guy A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.10.2016; Public Library of Science (PLoS)
• Subjects: Adult; Age; Autism; Biology and Life Sciences; DNA - chemistry; DNA - isolation & purification; DNA - metabolism; DNA Copy Number Variations; Female; Gene mutation; Genetic aspects; Genetics; Genomes; Genomics; Genotype; Germ-Line Mutation; Health risks; Humans; Male; Middle Aged; Mutation; Paternal Age; Pediatrics; Polymorphism, Single Nucleotide; Research and Analysis Methods; Schizophrenia; Sequence Analysis, DNA; Young Adult; Canada; Montreal Quebec Canada; Quebec Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164212

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.