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Science 301 (5633): 606-607

Copyright © 2003 by the American Association for the Advancement of Science

There's Something Curious About Paternal-Age Effects

James F. Crow

Gene mutation rates are higher in males than in females and increase with paternal age. In his Perspective, Crow explains unexpected results from a study of a congenital disease called Apert's syndrome in which the likelihood of a child developing the disease increases with the age of the father (Goriely et al.). The results of the new work imply that rather than sperm having a higher mutation rate, the harmful mutation may be positively selected perhaps because it confers some benefit within the cellular environment of the testis.

The author is in the Department of Genetics, University of Wisconsin, Madison, WI 53706, USA. E-mail: jfcrow{at}

Advanced paternal age and mortality of offspring under 5 years of age: a register-based cohort study.
S. K. Urhoj, L. N. Jespersen, M. Nissen, L. H. Mortensen, and A.- M. Nybo Andersen (2014)
Hum. Reprod. 29, 343-350
   Abstract »    Full Text »    PDF »
Fibroblast growth factor receptors, developmental corruption and malignant disease.
F. C. Kelleher, H. O'Sullivan, E. Smyth, R. McDermott, and A. Viterbo (2013)
Carcinogenesis 34, 2198-2205
   Abstract »    Full Text »    PDF »
Parental Age, Family Size, and Offspring's Risk of Childhood and Adult Acute Leukemia.
G. Larfors, H. Hallbook, and B. Simonsson (2012)
Cancer Epidemiol. Biomarkers Prev. 21, 1185-1190
   Abstract »    Full Text »    PDF »
Parents' Ages at Birth and Risk of Adult-onset Hematologic Malignancies Among Female Teachers in California.
Y. Lu, H. Ma, J. Sullivan-Halley, K. D. Henderson, E. T. Chang, C. A. Clarke, S. L. Neuhausen, D. W. West, L. Bernstein, and S. S. Wang (2010)
Am. J. Epidemiol. 171, 1262-1269
   Abstract »    Full Text »    PDF »
Schizophrenia: a common disease caused by multiple rare alleles.
J. M. McClellan, E. Susser, and M.-C. King (2007)
The British Journal of Psychiatry 190, 194-199
   Abstract »    Full Text »    PDF »
Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia.
A. Goriely, G. A. T. McVean, A. M. M. van Pelt, A. W. O'Rourke, S. A. Wall, D. G. de Rooij, and A. O. M. Wilkie (2005)
PNAS 102, 6051-6056
   Abstract »    Full Text »    PDF »
Paternal age and schizophrenia: a population based cohort study.
A. Sipos, F. Rasmussen, G. Harrison, P. Tynelius, G. Lewis, D. A Leon, and D. Gunnell (2004)
BMJ 329, 1070
   Abstract »    Full Text »    PDF »

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