title: Paternal lifestyle as a potential source of germline mutations transmitted to offspring.
abstract: Paternal exposure to high levels of radioactivity causes heritable germline minisatellite mutations. However, the effect of more general paternal exposures, such as cigarette smoking, on germline mutations remains unexplored. We analyzed two of the most commonly used minisatellite loci (CEB1 and B6.7) to identify germline mutations in blood samples of complete mother-father-child triads from the Norwegian Mother and Child Cohort Study (MoBa). The presence of mutations was subsequently related to general lifestyle factors, including paternal smoking before the partner became pregnant. Paternally derived mutations at the B6.7 locus (mutation frequency 0.07) were not affected by lifestyle. In contrast, high gross yearly income as a general measure of a healthy lifestyle coincided with low-mutation frequencies at the CEB1 locus (P=0.047). Income was inversely related to smoking behavior, and paternally derived CEB1 mutations were dose dependently increased when the father smoked in the 6 mo before pregnancy, 0.21 vs. 0.05 in smoking and nonsmoking fathers, respectively (P=0.061). These results suggest that paternal lifestyle can affect the chance of heritable mutations in unstable repetitive DNA sequences. To our knowledge, this is the first study reporting an effect of lifestyle on germline minisatellite mutation frequencies in a human population with moderate paternal exposures.
authors.affiliation: Department of Toxicology, School for Nutrition, Toxicology and Metabolism, Maastricht University, 6200MD Maastricht, The Netherlands.
authors.forename: Joost O
authors.initials: JO
authors.lastname: Linschooten
authors.forename: Nicole
authors.initials: N
authors.lastname: Verhofstad
authors.forename: Kristine
authors.initials: K
authors.lastname: Gutzkow
authors.forename: Ann-Karin
authors.initials: AK
authors.lastname: Olsen
authors.forename: Carole
authors.initials: C
authors.lastname: Yauk
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Oligschläger
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brunborg
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D018095:Germ-Line Mutation; D006801:Humans; D007182:Income; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008019:Life Style; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D059645:Mutation Rate; D009679:Nuclear Family; D010332:Paternal Behavior; D011247:Pregnancy; D011446:Prospective Studies; D012907:Smoking; D011795:Surveys and Questionnaires
chemical_list: C402395:HERC5 protein, human; D047908:Intracellular Signaling Peptides and Proteins
keywords: MoBa; cigarette smoking; genomic instability
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