Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line - PubMed (original) (raw)
. 2003 Aug 1;301(5633):643-6.
doi: 10.1126/science.1085710.
Affiliations
- PMID: 12893942
- DOI: 10.1126/science.1085710
Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line
Anne Goriely et al. Science. 2003.
Abstract
Observed mutation rates in humans appear higher in male than female gametes and often increase with paternal age. This bias, usually attributed to the accumulation of replication errors or inefficient repair processes, has been difficult to study directly. Here, we describe a sensitive method to quantify substitutions at nucleotide 755 of the fibroblast growth factor receptor 2 (FGFR2) gene in sperm. Although substitution levels increase with age, we show that even high levels originate from infrequent mutational events. We propose that these FGFR2 mutations, although harmful to embryonic development, are paradoxically enriched because they confer a selective advantage to the spermatogonial cells in which they arise.
Comment in
- Development. There's something curious about paternal-age effects.
Crow JF. Crow JF. Science. 2003 Aug 1;301(5633):606-7. doi: 10.1126/science.1088552. Science. 2003. PMID: 12893932 No abstract available.
Similar articles
- Development. There's something curious about paternal-age effects.
Crow JF. Crow JF. Science. 2003 Aug 1;301(5633):606-7. doi: 10.1126/science.1088552. Science. 2003. PMID: 12893932 No abstract available. - Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia.
Goriely A, McVean GA, van Pelt AM, O'Rourke AW, Wall SA, de Rooij DG, Wilkie AO. Goriely A, et al. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6051-6. doi: 10.1073/pnas.0500267102. Epub 2005 Apr 19. Proc Natl Acad Sci U S A. 2005. PMID: 15840724 Free PMC article. - Exclusive paternal origin of new mutations in Apert syndrome.
Moloney DM, Slaney SF, Oldridge M, Wall SA, Sahlin P, Stenman G, Wilkie AO. Moloney DM, et al. Nat Genet. 1996 May;13(1):48-53. doi: 10.1038/ng0596-48. Nat Genet. 1996. PMID: 8673103 - [From gene to disease; craniosynostosis syndromes due to FGFR2-mutation].
van Ravenswaaij-Arts CM, van den Ouweland AM, Hoogeboom AJ, Herbergs J, Pals G. van Ravenswaaij-Arts CM, et al. Ned Tijdschr Geneeskd. 2002 Jan 12;146(2):63-6. Ned Tijdschr Geneeskd. 2002. PMID: 11820058 Review. Dutch. - Cellular evidence for selfish spermatogonial selection in aged human testes.
Maher GJ, Goriely A, Wilkie AO. Maher GJ, et al. Andrology. 2014 May;2(3):304-14. doi: 10.1111/j.2047-2927.2013.00175.x. Epub 2013 Dec 19. Andrology. 2014. PMID: 24357637 Review.
Cited by
- Mechanisms of Germline Stem Cell Competition across Species.
Hodge RA, Bach EA. Hodge RA, et al. Life (Basel). 2024 Oct 1;14(10):1251. doi: 10.3390/life14101251. Life (Basel). 2024. PMID: 39459551 Free PMC article. Review. - SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.
Wood KA, Tong RS, Motta M, Cordeddu V, Scimone ER, Bush SJ, Maxwell DW, Giannoulatou E, Caputo V, Traversa A, Mancini C, Ferrero GB, Benedicenti F, Grammatico P, Melis D, Steindl K, Brunetti-Pierri N, Trevisson E, Wilkie AO, Lin AE, Cormier-Daire V, Twigg SR, Tartaglia M, Goriely A. Wood KA, et al. Am J Hum Genet. 2024 Sep 5;111(9):1953-1969. doi: 10.1016/j.ajhg.2024.07.006. Epub 2024 Aug 7. Am J Hum Genet. 2024. PMID: 39116879 Free PMC article. - Genetic variation across and within individuals.
Yu Z, Coorens THH, Uddin MM, Ardlie KG, Lennon N, Natarajan P. Yu Z, et al. Nat Rev Genet. 2024 Aug;25(8):548-562. doi: 10.1038/s41576-024-00709-x. Epub 2024 Mar 28. Nat Rev Genet. 2024. PMID: 38548833 Review. - Exploring FGFR3 Mutations in the Male Germline: Implications for Clonal Germline Expansions and Paternal Age-Related Dysplasias.
Moura S, Hartl I, Brumovska V, Calabrese PP, Yasari A, Striedner Y, Bishara M, Mair T, Ebner T, Schütz GJ, Sevcsik E, Tiemann-Boege I. Moura S, et al. Genome Biol Evol. 2024 Feb 1;16(2):evae015. doi: 10.1093/gbe/evae015. Genome Biol Evol. 2024. PMID: 38411226 Free PMC article. - Exploring the Micro-Mosaic Landscape of FGFR3 Mutations in the Ageing Male Germline and Their Potential Implications in Meiotic Differentiation.
Striedner Y, Arbeithuber B, Moura S, Nowak E, Reinhardt R, Muresan L, Salazar R, Ebner T, Tiemann-Boege I. Striedner Y, et al. Genes (Basel). 2024 Jan 30;15(2):191. doi: 10.3390/genes15020191. Genes (Basel). 2024. PMID: 38397181 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous