Skip to main content

Advertisement

SpringerLink
Log in

Genetic, environmental and epigenetic influences on variation in human tooth number, size and shape

  • Review Article
  • Published:
Odontology Aims and scope Submit manuscript

Abstract

The aim of this review is to highlight some key recent developments in studies of tooth number, size and shape that are providing better insights into the roles of genetic, environmental and epigenetic factors in the process of dental development. Advances in molecular genetics are helping to clarify how epigenetic factors influence the spatial and temporal regulation of the complex processes involved in odontogenesis. At the phenotypic level, the development of sophisticated systems for image analysis is enabling new dental phenotypes to be defined. The 2D and 3D data that are generated by these imaging systems can then be analysed with mathematical approaches, such as geometric morphometric analysis. By gathering phenotypic data and DNA from twins, it is now possible to use ‘genome-wide’ association studies and the monozygotic co-twin design to identify important genes in odontogenesis and also to clarify how epigenetic and environmental factors can affect this process. Given that many of the common dental anomalies affecting the human dentition are interrelated, apparently reflecting pleiotropic genetic effects, the discoveries and new directions described in this paper should have important implications for clinical dental practice in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kieser JA. Human adult odontometrics. Cambridge: Cambridge University Press; 1990.

    Google Scholar 

  2. Hillson S. Dental anthropology. Cambridge: Cambridge University Press; 1996.

    Google Scholar 

  3. Garn SM, Lewis AB, Kerewsky RS. Genetic, nutritional, and maturational correlates of dental development. J Dent Res. 1965;44:228–42.

    Article  PubMed  Google Scholar 

  4. Townsend GC, Brown T. Inheritance of tooth size in Australian Aboriginals. Am J Phys Anthropol. 1978;48:305–14.

    Article  PubMed  Google Scholar 

  5. Townsend GC, Brown T. Heritability of permanent tooth size. Am J Phys Anthropol. 1978;49:497–504.

    Article  PubMed  Google Scholar 

  6. Wilson DF, Brown KA. Forensic odontology. In: Prabhu SR, Wilson DF, Daftary DK, Johnson NW, editors. Oral diseases in the tropics. New York: Oxford University Press; 1992. p. 752–64.

    Google Scholar 

  7. Demirjian A. Dentition. In: Falkner F, Tanner JM, editors. Human growth, 2 postnatal growth. New York: Plenum Press; 1978. p. 413–44.

    Google Scholar 

  8. Townsend GC. Heritability of deciduous tooth size in Australian Aboriginals. Am J Phys Anthropol. 1980;53:297–300.

    Article  PubMed  Google Scholar 

  9. Tucker A, Sharpe P. The cutting-edge of mammalian development: how the embryo makes teeth. Nat Rev Genet. 2004;5:499–508.

    Article  PubMed  Google Scholar 

  10. Sperber GH. The genetics of odontogenesis: implications in dental anthropology and palaeo-odontology. Dent Anthropol. 2004;17:1–7.

    Google Scholar 

  11. Thesleff I. The genetic basis of tooth development and dental defects. Am J Med Genet. 2006;140A:2530–5.

    Article  Google Scholar 

  12. Townsend G, Hughes T, Luciano M, Brook A. Genetic and environmental influences on human dental variation: limitations and advantages of studies involving twins. Arch Oral Biol. 2009;54:S45–51.

    Article  PubMed  Google Scholar 

  13. Townsend G, Hughes T, Bockmann M, Smith R, Brook A. How studies of twins can inform our understanding of dental morphology. In: Koppe T, Meyer G, Alt KW, editors. Comparative Dental Morphology. Frontiers of Oral Biology, vol 13. Basel: Karger; 2009. p.136–41.

  14. Barros SP, Offenbacher S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res. 2009;88:400–8.

    Article  PubMed  Google Scholar 

  15. Brook AH, Brook O’Donnell M. Modelling the complexity of the dentition. In: Townsend G, Kanazawa E, Takayama H, editors. New directions in dental anthropology: paradigms, methodologies and outcomes. Adelaide: University of Adelaide Press; 2011 (in press).

  16. Hughes T, Townsend G. Genes for teeth—drawing inference from family data. In: Townsend G, Kanazawa E, Takayama H, editors. New directions in dental anthropology: paradigms, methodologies and outcomes. Adelaide: University of Adelaide Press; 2011 (in press).

  17. Brook AH. Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development. Arch Oral Biol. 2009;54S:S3–17.

    Article  Google Scholar 

  18. Jernvall J, Thesleff I. Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev. 2000;92:19–29.

    Article  PubMed  Google Scholar 

  19. Salazar-Ciudad I, Jernvall J. A gene network model accounting for development and evolution of mammalian teeth. Proc Natl Acad Sci USA. 2002;99:8116–20.

    Article  PubMed  Google Scholar 

  20. Lesot H, Brook A. Epithelial histogenesis during tooth development. Arch Oral Biol. 2009;54:S25–33.

    Article  PubMed  Google Scholar 

  21. Cai J, Cho S-W, Kim J-Y, Lee M-J, Cha Y-G, Jung H-S. Patterning the size and number of tooth and its cusps. Dev Biol. 2007;304:499–507.

    Article  PubMed  Google Scholar 

  22. Jernvall J, Jung HS. Genotype, phenotype, and developmental biology of molar tooth characteristics. Am J Phys Anthropol. 2000;31:171–90.

    Article  PubMed  Google Scholar 

  23. Salazar-Ciudad I, Jernvall J, Newman SA. Mechanisms of pattern formation in development and evolution. Development. 2003;130:2027–37.

    Article  PubMed  Google Scholar 

  24. Ishida K, Murofushi M, Nakao K, Ogawa M, Tsuji T. The regulation of tooth morphogenesis is associated with epithelial cell proliferation and the expression of Sonic hedgehog through epithelial-mesenchymal interactions. Biochem Biophys Res Commun. 2011;405(3):455–61. doi:10.1016/j.bbrc.2011.01.052.

    Article  PubMed  Google Scholar 

  25. Alvesalo L. Human sex chromosomes in oral and craniofacial growth. Arch Oral Biol. 2009;54:S18–24.

    Article  PubMed  Google Scholar 

  26. Foster CL, Harris EF. Discriminatory effectiveness of crown indexes—tests between American blacks and whites. Dent Anthropol. 2009;22:85–92.

    Google Scholar 

  27. Townsend GC. Intercuspal distances of maxillary premolar teeth in Australian Aboriginals. J Dent Res. 1985;64:443–6.

    Article  PubMed  Google Scholar 

  28. Townsend G, Richards L, Hughes T. Molar intercuspal dimensions: genetic input to phenotypic variation. J Dent Res. 2003;82:350–5.

    Article  PubMed  Google Scholar 

  29. Brook AH, Pitts NB, Renson CE. Determination of tooth dimensions from study casts using an image analysis system. J Int Assoc Dent Child. 1983;14:55–60.

    PubMed  Google Scholar 

  30. Brook AH, Smith RN, Elcock C, Al-Sharood M, Shah A, Karmo M. The measurement of tooth morphology: development and evaluation of a new image analysis system. In: Mayhall J, Heikkinen T, editors. Proceedings of the 11th International Symposium on Dental Morphology. Oulu: Oulu University Press; 1999. p. 380–7.

    Google Scholar 

  31. Smith R, Zaitoun H, Coxon T, Karmo M, Kaur G, Townsend G, Harris E, Brook A. Defining new dental phenotypes using 3-D image analysis to enhance discrimination and insights into biological processes. Arch Oral Biol. 2009;54S:S118–25.

    Article  Google Scholar 

  32. Brook AH, Pitts NB, Yau F. An image analysis system for the determination of tooth dimensions from study casts: comparison with manual measurement of mesio-distal diameter. J Dent Res. 1986;65:428–31.

    Article  PubMed  Google Scholar 

  33. Kondo S, Townsend G. Associations between Carabelli trait and cusp areas in human permanent maxillary first molars. Am J Phys Anthropol. 2006;129:196–203.

    Article  PubMed  Google Scholar 

  34. Hunter JP, Guatelli-Steinberg D, Weston TC, Durner R, Betsinger TK. Model of tooth morphogenesis predicts Carabelli cusp expression, size, and symmetry in humans. PloS ONE. 2010;5(7):e11844. doi:10.1371/journal.pone.0011844.

  35. Mayhall J, Townsend G. The changing crown morphology of maxillary first molars and its effect on the efficiency of mastication. In: Zadzinska E, editor. Current trends in dental morphology research. Refereed proceedings, 13th International Symposium on Dental Morphology. Poland: University of Lodz; 2005. p. 97–104.

    Google Scholar 

  36. Aas IHM. Variability of a dental morphological trait. Acta Odontol Scand. 1983;41:257–63.

    Article  PubMed  Google Scholar 

  37. Skinner MM, Wood BA, Boesch C, Olejniczak AJ, Rosas A, Smith TM, Hublin J-J. Dental trait expression at the enamel-dentine junction of lower molars in extant and fossil hominoids. J Hum Evol. 2008;54:173–86.

    Article  PubMed  Google Scholar 

  38. Gordon LM, Joester D. Nanoscale chemical tomography of buried organic-inorganic interfaces in the chiton tooth. Nature. 2011;469:194–8.

    Article  PubMed  Google Scholar 

  39. Houle D, Govindaraju DR, Omholt S. Phenomics: the next challenge. Nat Rev Genet. 2010;11:855–66.

    Article  PubMed  Google Scholar 

  40. Harris EF, Bailit HL. A principal components analysis of human odontometrics. Am J Phys Anthropol. 1988;75:87–99.

    Article  PubMed  Google Scholar 

  41. Townsend GC, Brown T. Family studies of tooth size factors in the permanent dentition. Am J Phys Anthropol. 1979;50:183–90.

    Article  PubMed  Google Scholar 

  42. Abe K, Suzuki A, Takahama Y. Prediction of coronal size of third molars by factor and multiple regression analyses. Am J Orthod Dentofac Orthop. 1996;109:79–85.

    Article  Google Scholar 

  43. Khalef K, Smith RN, Elcock C, Brook AH. Multiple crown variables of the upper incisors in patients with supernumerary teeth compared with controls. Arch Oral Biol. 2009;54:S71–8.

    Article  Google Scholar 

  44. Rohlf FJ. Creases as morphometric characters. In: MacLeod N, Forey PL, editors. Morphology, shape and phylogeny. London: Taylor & Francis; 2002.

    Google Scholar 

  45. Rohlf FJ, Bookstein FL. Computing the uniform component of shape variation. Syst Biol. 2003;52:66–9.

    Article  PubMed  Google Scholar 

  46. Zelditch ML, Swiderski DL, Sheets HD. Fink WL. Geometric morphometrics for biologists: a primer. Elsevier Academic Press, San Diego; 2004.

    Google Scholar 

  47. Kendall D. The diffusion of shape. Adv Appl Probab. 1977;9:428–30.

    Article  Google Scholar 

  48. Klingenberg CP, Leamy LJ. Quantitative genetics of geometric shape in the mouse mandible. Evolution. 2001;55:2342–52.

    PubMed  Google Scholar 

  49. Robinson DL, Blackwell P, Stillman E, Brook AH. Planar Procrustes analysis of tooth shape. Arch Oral Biol. 2001;46:191–9.

    Article  PubMed  Google Scholar 

  50. Klingenberg CP. Evolution and development of shape: integrating quantitative approaches. Nat Rev Genet. 2010;11:623–35.

    PubMed  Google Scholar 

  51. Klingenberg CP, Debat V, Roff DA. Quantitative genetics of shape in cricket wings: developmental integration in a functional structure. Evolution. 2010;64:2935–51.

    PubMed  Google Scholar 

  52. Bernal V. Size and shape analysis of human molars: comparing traditional and geometric morphometric techniques. J Hum Evol. 2007;58:279–96.

    Google Scholar 

  53. Gómez-Robles A, Matinón-Torres M, Bermúdez de Castro JM, Prado L, Sarmiento S, Arsuaga JL. Geometric morphometric analysis of the crown morphology of the lower first premolar of hominins, with special attention to Pleistocene. J Hum Evol. 2008;55:627–38.

    Article  PubMed  Google Scholar 

  54. Martinόn-Torres M, Bastir M, Bermudéz de Castro JM, Gómez A, Sarmiento S, Muela A, Arsuaga JL. Hominin lower second premolar morphology: evolutionary inferences through geometric morphometric analysis. J Hum Evol. 2006;50:523–33.

    Article  Google Scholar 

  55. Robinson DL, Blackwell PG, Stillman EC, Brook AH. Impact of landmark reliability on the planar Procrustes analysis of tooth shape. Arch Oral Biol. 2002;47:545–54.

    Article  PubMed  Google Scholar 

  56. Klingenberg C. MORPHOJ: an integrated software package for geometric morphometrics. Mol Ecol Resour. 2011;11:353–7.

    Article  PubMed  Google Scholar 

  57. Dempsey PJ, Townsend GC, Martin NG, Neale MC. Genetic covariance structure of incisor crown size in twins. J Dent Res. 1995;74:1389–98.

    Article  PubMed  Google Scholar 

  58. Hughes T, Dempsey P, Richards L, Townsend G. Genetic analysis of deciduous tooth size in Australian twins. Arch Oral Biol. 2000;45:997–1004.

    Article  PubMed  Google Scholar 

  59. Dempsey P, Townsend GC. Genetic and environmental contributions to variation in human tooth size. Heredity. 2001;86:685–93.

    Article  PubMed  Google Scholar 

  60. Higgins D, Hughes T, James H, Townsend G. Strong genetic influence on hypocone expression of permanent maxillary molars in South Australian twins. Dental Anthropol. 2009;22:1–7.

    Google Scholar 

  61. Waddington CH. The strategy of genes: a discussion of some aspects of theoretical biology. London: Allen & Unwin; 1957.

    Google Scholar 

  62. Townsend G, Richards L, Hughes T, Pinkerton S, Schwerdt W. Epigenetic influences may explain dental differences in monozygotic twin pairs. Aust Dent J. 2005;50:95–100.

    Article  PubMed  Google Scholar 

  63. Suda N, Hattori M, Kosaki K, Banshodani A, Kozai K, Tanimoto K, Moriyama K. Correlation between genotype and supernumerary tooth formation in cleidocranial dysplasia. Orthod Craniofac Res. 2010;13:197–202.

    Article  PubMed  Google Scholar 

  64. Brook AH. A unifying aetiological explanation for anomalies of human tooth number and size. Arch Oral Biol. 1984;29:373–8.

    Article  PubMed  Google Scholar 

  65. Sofaer JA, Chung CS, Niswander JD, Runck DW. Developmental interaction, size and agenesis among permanent maxillary incisors. Hum Biol. 1978;43:36–45.

    Google Scholar 

  66. Yamada H, Kondo S, Hanamura H, Townsend GC. Tooth size in individuals with congenitally missing teeth: a study of Japanese males. Anthropol Sci. 2010;118:87–93.

    Article  Google Scholar 

  67. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661–8.

    Article  Google Scholar 

  68. Pillas D, Hoggart CJ, Evans DM, O’Reilly PF, Sipila K, Lähdesmäki R, et al. Genome-wide association study reveals multiple loci associated with primary tooth development during infancy. PLoS Genetics. 2010;6:1–7.

    Article  Google Scholar 

  69. Hughes T, Bockmann M, Seow K, Gotjamanos T, Gully N, Richards L, Townsend G. Strong genetic control of emergence of human primary incisors. J Dent Res. 2007;86:1160–5.

    Article  PubMed  Google Scholar 

  70. Bockmann M, Hughes T, Townsend G. Genetic modelling of primary tooth emergence: a study of Australian twins. Twin Res Hum Genet. 2010;13:573–81.

    Article  PubMed  Google Scholar 

  71. Kimura R, Yamaguchi T, Takeda M, Kondo O, Toma T, Haneji K, et al. A common variation in EDAR is a genetic determinant of shovel-shaped incisors. Am J Hum Genet. 2009;85:528–35.

    Article  PubMed  Google Scholar 

  72. Mustonen T, Pispa J, Mikkola ML, Pummila M, Kangas AT, Pakkasjarvi L, et al. Stimulation of ectodermal organ development by Ectodysplasin-A1. Dev Biol. 2003;259:123–36.

    Article  PubMed  Google Scholar 

  73. Tucker AS, Headon DJ, Courtney JM, Overbeek P, Sharpe PT. The activation level of the TFN family receptor, Edar, determines cusp number and tooth number during development. Dev Biol. 2004;268:185–94.

    Article  PubMed  Google Scholar 

  74. Tucker AS, Sharpe PT. Molecular genetics of tooth morphogenesis and patterning; the right shape in the right place. J Dent Res. 1999;78:826–34.

    Article  PubMed  Google Scholar 

  75. Kangas AT, Evans AR, Thesleff I, Jernvall J. Nonindependence of mammalian dental characters. Nature. 2004;432:211–4.

    Article  PubMed  Google Scholar 

  76. Kotsomitis N, Freer TJ. Inherited dental anomalies and abnormalities. ASDC J Dent Child. 1997;64:405–8.

    PubMed  Google Scholar 

  77. Baccetti T. A controlled study of associated dental anomalies. Angle Orthod. 1998;68:267–74.

    PubMed  Google Scholar 

  78. Brook AH, Elcock C, Al-Sharood MH, McKeown HF, Khalaf K, Smith RN. Further studies of a model for the etiology of anomalies of tooth number and size in humans. Connect Tissue Res. 2002;43:289–95.

    PubMed  Google Scholar 

  79. Peck S, Peck L, Kataja M. Concomitant occurrence of canine malposition and tooth agenesis: evidence of orofacial genetic fields. Am J Orthod Dentofacial Orthop. 2002;122:657–60.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the financial support of the NHMRC of Australia, the Australian Dental Research Foundation, the Financial Markets Foundation for Children, the University of Adelaide and Colgate Australia. Our sincere thanks to the twins and their families who have participated in our studies and to the NHRMC Twin Registry and the Australian Multiple Birth Association. The micro-CT work was performed at the South Australian node of the Australian National Fabrication Facility under the National Collaborative Research Infrastructure Strategy.

Author information

Authors and Affiliations

  1. School of Dentistry, The University of Adelaide, Adelaide, 5005, South Australia

    Grant Townsend, Michelle Bockmann, Toby Hughes & Alan Brook

  2. Centre for Orofacial Research and Learning (CORAL), Adelaide, South Australia

    Grant Townsend, Michelle Bockmann, Toby Hughes & Alan Brook

  3. International Collaborating Network in Oro-facial Genetics and Development, Adelaide, South Australia

    Grant Townsend, Michelle Bockmann, Toby Hughes & Alan Brook

  4. Dental Institute, Queen Mary University of London, London, UK

    Alan Brook

Authors
  1. Grant Townsend
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michelle Bockmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toby Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alan Brook
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Grant Townsend.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Townsend, G., Bockmann, M., Hughes, T. et al. Genetic, environmental and epigenetic influences on variation in human tooth number, size and shape. Odontology 100, 1–9 (2012). https://doi.org/10.1007/s10266-011-0052-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10266-011-0052-z

Keywords

Search

Navigation