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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.

SUBMITTER: Girard SL

PROVIDER: S-EPMC5056704 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Girard Simon L SL Bourassa Cynthia V CV Lemieux Perreault Louis-Philippe LP Legault Marc-André MA Barhdadi Amina A Ambalavanan Amirthagowri A Brendgen Mara M Vitaro Frank F Noreau Anne A Dionne Ginette G Tremblay Richard E RE Dion Patrick A PA Boivin Michel M Dubé Marie-Pierre MP Rouleau Guy A GA

PloS one 20161010 10

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 germ ...[more]

PMID: 27723766

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