Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 9, 2016, Pages 2454-2459

  Maher, Geoffrey J ^a   McGowan, Simon J ^a   Giannoulatou, Eleni ^a,c   Verrill, Clare ^b   Goriely, Anne ^a   Wilkie, Andrew O M ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b OXFORD UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^c VICTOR CHANG CARDIAC RESEARCH INSTITUTE   (Australia)

Author keywords

Germline; Mutation; Selfish selection; Seminiferous tubule; Testis

Indexed keywords

DNA; FIBROBLAST GROWTH FACTOR RECEPTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR 3; MELANOMA ANTIGEN A4; PROTEIN; PROTEIN KINASE B; PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE SHP 2; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CELL SURVIVAL; DNA SEQUENCE; GAIN OF FUNCTION MUTATION; GENE AMPLIFICATION; GERM CELL; GERMLINE MUTATION; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; MICRODISSECTION; MICROSCOPIC ANATOMY; MUTATION; ONCOGENE H RAS; ONCOGENE K RAS; POINT MUTATION; PREVALENCE; PRIORITY JOURNAL; SEMINIFEROUS TUBULE; SIGNAL TRANSDUCTION; SPERMATOGENESIS; METABOLISM;

HUMANS; MALE; MUTATION; SEMINIFEROUS TUBULES;

EID: 84959535644     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1521325113     Document Type: Article

References (55)

1. Deciphering Developmental Disorders Study (2015) Large-scale discovery of novel genetic causes of developmental disorders. Nature 519:223-228.
2. Iossifov I, et al. (2014) The contribution of de novo coding mutations to autism spectrum disorder. Nature 515(7526):216-221.
3. O'Roak BJ, et al. (2014) Recurrent de novo mutations implicate novel genes underlying simplex autism risk. Nat Commun 5:5595.
4. Hoischen A, Krumm N, Eichler EE (2014) Prioritization of neurodevelopmental disease genes by discovery of new mutations. Nat Neurosci 17(6):764-772.
5. Kong A, et al. (2012) Rate of de novo mutations and the importance of father's age to disease risk. Nature 488(7412):471-475.
6. Besenbacher S, et al. (2015) Novel variation and de novo mutation rates in population- wide de novo assembled Danish trios. Nat Commun 6:5969.
7. Paul C, Robaire B (2013) Ageing of the male germ line. Nat Rev Urol 10(4):227-234.
8. Paniagua R, Nistal M, Amat P, Rodriguez MC, Martin A (1987) Seminiferous tubule involution in elderly men. Biol Reprod 36(4):939-947.
9. Miething A (2005) Arrested germ cell divisions in the ageing human testis. Andrologia 37(1):10-16.
10. Goriely A, Wilkie AOM (2012) Paternal age effect mutations and selfish spermatogonial selection: Causes and consequences for human disease. Am J Hum Genet 90(2):175-200.
11. Qin J, et al. (2007) The molecular anatomy of spontaneous germline mutations in human testes. PLoS Biol 5(9):e224.
12. Choi SK, Yoon SR, Calabrese P, Arnheim N (2008) A germ-line-selective advantage rather than an increased mutation rate can explain some unexpectedly common human disease mutations. Proc Natl Acad Sci USA 105(29):10143-10148.
13. Choi SK, Yoon SR, Calabrese P, Arnheim N (2012) Positive selection for new disease mutations in the human germline: Evidence from the heritable cancer syndrome multiple endocrine neoplasia type 2B. PLoS Genet 8(2):e1002420.
14. Shinde DN, et al. (2013) New evidence for positive selection helps explain the paternal age effect observed in achondroplasia. Hum Mol Genet 22(20):4117-4126.
15. Yoon SR, et al. (2013) Age-dependent germline mosaicism of the most common Noonan syndrome mutation shows the signature of germline selection. Am J Hum Genet 92(6):917-926.
16. Giannoulatou E, et al. (2013) Contributions of intrinsic mutation rate and selfish selection to levels of de novo HRAS mutations in the paternal germline. Proc Natl Acad Sci USA 110(50):20152-20157.
17. Wilkie AOM, et al. (1995) Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 9(2):165-172.
18. Tartaglia M, et al. (1997) Jackson-Weiss syndrome: Identification of two novel FGFR2 missense mutations shared with Crouzon and Pfeiffer craniosynostotic disorders. Hum Genet 101(1):47-50.
19. Schaefer F, Anderson C, Can B, Say B (1998) Novel mutation in the FGFR2 gene at the same codon as the Crouzon syndrome mutations in a severe Pfeiffer syndrome type 2 case. Am J Med Genet 75(3):252-255.
20. Khonsari RH, et al. (2012) Central nervous system malformations and deformations in FGFR2-related craniosynostosis. Am J Med Genet A 158A(11):2797-2806.
21. Bellus GA, et al. (1995) Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet 56(2):368-373.
22. Tavormina PL, et al. (1995) Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nat Genet 9(3):321-328.
23. Rousseau F, et al. (1996) Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1). Hum Mol Genet 5(4):509-512.
24. Carlson KM, et al. (1994) Parent-of-origin effects in multiple endocrine neoplasia type 2B. Am J Hum Genet 55(6):1076-1082.
25. Tartaglia M, Gelb BD, Zenker M (2011) Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab 25(1):161-179.
26. Goriely A, et al. (2009) Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors. Nat Genet 41(11):1247-1252.
27. Goriely A, McVean GAT, Röjmyr M, Ingemarsson B, Wilkie AOM (2003) Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science 301(5633):643-646.
28. Goriely A, et al. (2005) Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia. Proc Natl Acad Sci USA 102(17):6051-6056.
29. Yoon SR, et al. (2009) The ups and downs of mutation frequencies during aging can account for the Apert syndrome paternal age effect. PLoS Genet 5(7):e1000558.
30. Aubry F, et al. (2001) MAGE-A4, a germ cell specific marker, is expressed differentially in testicular tumors. Cancer 92(11):2778-2785.
31. von Kopylow K, Staege H, Schulze W, Will H, Kirchhoff C (2012) Fibroblast growth factor receptor 3 is highly expressed in rarely dividing human type A spermatogonia. Histochem Cell Biol 138(5):759-772.
32. Lee J, et al. (2007) Akt mediates self-renewal division of mouse spermatogonial stem cells. Development 134(10):1853-1859.
33. Lee J, et al. (2009) Genetic reconstruction of mouse spermatogonial stem cell selfrenewal in vitro by Ras-cyclin D2 activation. Cell Stem Cell 5(1):76-86.
34. Lim J, et al. (2012) Selfish spermatogonial selection: Evidence from an immunohistochemical screen in testes of elderly men. PLoS One 7(8):e42382.
35. Maher GJ, Goriely A, Wilkie AOM (2014) Cellular evidence for selfish spermatogonial selection in aged human testes. Andrology 2(3):304-314.
36. Forbes SA, et al. (2015) COSMIC: Exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res 43(Database issue, D1):D805-D811.
37. Vogelstein B, et al. (2013) Cancer genome landscapes. Science 339(6127):1546-1558.
38. Rahman N (2014) Realizing the promise of cancer predisposition genes. Nature 505(7483):302-308.
39. Johnsen SG (1970) Testicular biopsy score count-a method for registration of spermatogenesis in human testes: Normal values and results in 335 hypogonadal males. Hormones 1(1):2-25.
40. Nakata H, et al. (2015) Three-dimensional structure of seminiferous tubules in the adult mouse. J Anat 227(5):686-694.
41. Klein AM, Nakagawa T, Ichikawa R, Yoshida S, Simons BD (2010) Mouse germ line stem cells undergo rapid and stochastic turnover. Cell Stem Cell 7(2):214-224.
42. Hara K, et al. (2014) Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states. Cell Stem Cell 14(5):658-672.
43. Martin LA, Assif N, Gilbert M, Wijewarnasuriya D, Seandel M (2014) Enhanced fitness of adult spermatogonial stem cells bearing a paternal age-associated FGFR2 mutation. Stem Cell Rep 3(2):219-226.
44. Glass J (2005) Testes and epididymes. Gray's Anatomy: The Anatomical Basis of Clinical Practice, ed Standring S (Churchill Livingston, Edinburgh), 39th Ed, pp 1304-1310.
45. Juul A, et al. (2007) Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene: Case report. Hum Reprod 22(7):1907-1911.
46. Naski MC, Wang Q, Xu J, Ornitz DM (1996) Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia. Nat Genet 13(2):233-237.
47. Goriely A, McGrath JJ, Hultman CM, Wilkie AOM, Malaspina D (2013) "Selfish spermatogonial selection": A novel mechanism for the association between advanced paternal age and neurodevelopmental disorders. Am J Psychiatry 170(6):599-608.
48. Jaiswal S, et al. (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371(26):2488-2498.
49. McKerrell T, et al.; Understanding Society Scientific Group (2015) Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Reports 10(8):1239-1245.
50. Hafner C, et al. (2007) Spectrum of FGFR3 mutations in multiple intraindividual seborrheic keratoses. J Invest Dermatol 127(8):1883-1885.
51. Martincorena I, et al. (2015) High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348(6237):880-886.
52. Koboldt DC, et al. (2012) VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 22(3):568-576.
53. Wang K, Li M, Hakonarson H (2010) ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38(16):e164.
54. Exome Variant Server, NHLBI GO Exome Sequencing Project (ESP), Seattle, WA. Available at evs.gs.washington.edu/EVS/. Accessed January 31, 2015.
55. Abecasis GR, et al.; 1000 Genomes Project Consortium (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491(7422):56-65.