An Invariant Approach to the Study of Fluctuating Asymmetry: Developmental Instability in a Mouse Model for Down Syndrome

  • Joan T. Richtsmeier
  • Theodore M. ColeIII
  • Subhash R. Lele

Summary and Conclusions

We have presented a novel method for statistical comparison of FA. The advantages of our method include:
  1. 1.

    the straightforward inclusion of three-dimensional data;

     
  2. 2.

    the lack of superimposition, so that the user does not need to arbitrarily select a fitting criterion;

     
  3. 3.

    identification of significant differences in FA by bootstrap confidence intervals;

     
  4. 4.

    presentation of local measures of FA, enabling identification of the affected anatomical structures and the proposal of testable developmental hypotheses.

     

The results of our analysis of FA in the Ts1Cje mouse provide preliminary support for the amplified DI hypothesis and provide the basis for a model of the interplay of dysmorphology and FA in aneuploidy that can be further explored in studies of development.

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References

  1. Antonarakis, S. E., 1991, Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of DNA polymorphisms. Down Syndrome Collaborative Group, N. Engl. J. Med. 324:872–876.CrossRefGoogle Scholar
  2. Antonarakis, S. E., Petersen, M. B., McInnis, M. G., Adelsberger, P. A., Schinzel, A. A., Binkert, F. et al., 1992, The meiotic stage of nondisjunction in trisomy 21: Determination by using DNA polymorphisms, Am. J. Hum. Genet. 50:544–550.Google Scholar
  3. Antonarakis, S. E., Avramopoulos, D., Blouin, J. L., Talbot, C. C., Jr., and Schinzel, A. A., 1993, Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age, Nat. Genet. 3:146–150.CrossRefGoogle Scholar
  4. Auffray, J.-C., Alibert, P., Renaud, S., Orth, A., and Bonhomme, F., 1996, Fluctuating asymmetry in Mus musculus subspecific hybridization: Traditional and Procrustes comparative approach, in: Advances in Morphometrics, L. Marcus, M. Corti, A. Loy, G. J. P. Naylor, and D. E. Slice, eds., Plenum Press, New York, pp. 275–283.Google Scholar
  5. Baxter, L. L., Moran, T. H., Richtsmeier, J. T., Troncoso, J., and Reeves, R. H., 2000, Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse, Hum. Mol. Genet. 9:195–202.CrossRefGoogle Scholar
  6. Bookstein, F., 1991, Morphometric Tools for Landmark Data: Geometry and Biology, Cambridge University Press, Cambridge.Google Scholar
  7. Chapman, R., 1990, Conventional Procrustes approaches, in: Proceedings of the Michigan Morphometrics Workshop, F. J. Rohlf and F. L. Bookstein, eds., University of Michigan Museum of Zoology, Ann Arbor, pp. 251–267.Google Scholar
  8. Cole, T. M. III, 2001, Chapter 7. Further applications of EDMA, in: An Invariant Approach to the Statistical Analysis of Shapes, S. Lele and J. T. Richtsmeier, eds., Chapman and Hall/CRC Press, London, pp. 263–284.Google Scholar
  9. Davison, A. C. and Hinkley, D. V., 1997, Bootstrap Methods and their Applications, Cambridge University Press, Cambridge.Google Scholar
  10. Davisson, M., Schmidt, C., Reeves, N., Irving, E., Akeson, E., Harris, B. et al., 1993, Segmental trisomy as a mouse model for Down Syndrome, Prog. Clin. Biol. Res. 384:117–133.Google Scholar
  11. Delabar, J.-M., Theophile, D., Rahmani, Z., Chettouh, Z., Blouin, J.-L., Prieut, M., Noel, B., and Sinet, P.-M., 1993, Molecular mapping of twenty-four features of Down syndrome on Chromosome 21, Eur. J. Hum. Genet. 1:114–124.Google Scholar
  12. DeLeon, V. B., 2004, Fluctuating Asymmetry in the Human Craniofacial Skeleton: Effects of Sexual Dimorphism, Stress, and Developmental Anomalies, PhD Thesis, Center for Functional Anatomy & Evolution, Johns Hopkins University.Google Scholar
  13. Efron, B. and Tibshirani, R., 1993, An Introduction to the Bootstrap. Chapman & Hall, New York.Google Scholar
  14. Fuller, R. and Houle, D., 2002, Detecting genetic variation in devleopmental instability by artificial selection on fluctuating asymmetry, J. Evol. Biol. 15:954–960.CrossRefGoogle Scholar
  15. Greber-Platzer, S., Schatzmann-Turhani, D., Wollenek, G., and Lubec, G., 1999, Evidence against the current hypothesis of “gene dosage effects” of trisomy 21: ets-2, encoded on chromosome 21 is not overexpressed in hearts of patients with Down syndrome, Biochem. Biophys. Res. Commun. 254:395–399.CrossRefGoogle Scholar
  16. Hall, B., 1965, Delayed ontogenesis in human trisomy syndromes, Hereditas 52:334–344.CrossRefGoogle Scholar
  17. Hall, P. and Martin, M., 1988, On the bootstrap and two-sample problems, Austral. J. Stat. 30A:179–192.Google Scholar
  18. Hallgrímmson, B. and Hall, B., 2002, Modularity within and among limbs: Implications for evolutionary divergence in fore-and hind limb morphology in primates, Am. J. Phys. Anthropol. Suppl. 34:81 (abstract).Google Scholar
  19. Hattori, M., Fujiyama, A., Taylor, T. D., Watanabe, H., Yada, T., Park, H. S. et al., 2000, The DNA sequence of human chromosome 21, Nature 405:311–319.CrossRefGoogle Scholar
  20. Hill, C., Reeves, R. H., Epstein, C. J., Valeri, C. J., Lindsay, E., Baxter, L. L. Cole, T. M., Richtsmeier, JT, 2003, Developmental instability and skeletal phenotypes in Down syndrome, Am. J. Phys. Anthropol. Suppl. 36:114 (abstract).Google Scholar
  21. Kirschner, M. and Gerhart, J., 1998, Evolvability, Proc. Natl. Acad. Sci. USA 95:8420–8427.CrossRefGoogle Scholar
  22. Kisling, E., 1966, Cranial Morphology in Down’s Syndrome: A Comparative Roentgencephalometric Study in Adult Males, Munksgaard, Copenhagen.Google Scholar
  23. Klingenberg, C., 2003, A developmental perspective on developmental instability: Theory, models and mechanisms, in: Developmental Instability: Causes and Consequences, M. Polak, ed., Oxford University Press, New York, pp. 427–442.Google Scholar
  24. Klingenberg, C. and McIntyre, G., 1998, Geometric morphometrics of developmental instability: Analyzing patterns of fluctuating asymmetry with Procrustes methods, Evolution 52:1363–1375.CrossRefGoogle Scholar
  25. Klingenberg, C. P., Barluenga, M., and Meyer, A., 2002, Shape analysis of symmetric structures: Quantifying variation among individuals and asymmetry, Evolution 56:1909–1920.Google Scholar
  26. Kohn, L. and Cheverud, J., 1992, Calibration, validation, and evaluation of scanning systems: Anthropmetric imaging system repeatability, in: Electronic Imaging of the Human Body Workshop, CSERIAC, Dayton, OH.Google Scholar
  27. Korenberg, R., 1991, Down syndrome phenotypic mapping. Progress in clinical Biology, Research 373:43–53.Google Scholar
  28. Korenberg, J. R., Kawashima, H., Pulst, S. M., Ikeuchi, T., Ogasawara, N., Yamamoto, K. et al., 1990, Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype, Am. J. Hum. Genet. 47:236–246.Google Scholar
  29. Korenberg, J., Chen, X., Schipper, R., Sun, Z., Gonsky, R., Gerwehr, S. et al., 1994, Down syndrome phenotypes: The consequences of chromosomal imbalance, Proc. Natl. Acad. Sci. USA 91:4997–5001.Google Scholar
  30. Lande, R., 1977, On comparing coefficients of variation, Syst. Zool. 26:214–217.CrossRefGoogle Scholar
  31. Lele, S., 1991, Some comments on coordinate free and scale invariant methods in morphometrics, Am. J. Phys. Anthropol. 85:407–418.CrossRefGoogle Scholar
  32. Lele, S., 1993, Euclidean distance matrix analysis (EDMA) of landmark data: Estimation of mean form and mean form difference, Math. Geol. 25:573–602.CrossRefGoogle Scholar
  33. Lele, S. and McCulloch, C., 2002, Invariance and morphometrics, J. Am. Stat. Assoc. 971:796–806.CrossRefGoogle Scholar
  34. Lele, S. and Richtsmeier, J., 1990, Statistical models in morphometrics: Are they realistic? Syst. Zool. 39:60–69.CrossRefGoogle Scholar
  35. Lele, S. and Richtsmeier, J. T., 1992, On comparing biological shapes: Detection of influential landmarks, Am. J. Phys. Anthropol. 87:49–65.CrossRefGoogle Scholar
  36. Lele, S. and Richtsmeier, J., 2001, An Invariant Approach to the Statistical Analysis of Shapes, Chapman and Hall/CRC Press, London.Google Scholar
  37. Levinson, A., Friedman, A., and Stamps, F., 1955, Variability of mongolism, Pediatrics 16:43.Google Scholar
  38. Marcus, L., Corti, M., Loy, A., Naylor, G. J. P., and Slice, D. E., 1996, Advances in Morphometrics, Plenum, New York.Google Scholar
  39. Mardia, K., Bookstein, F., and Moreton, I., 2000, Statistical assessment of bilateral symmetry of shapes, Biometrika 87:285–300.CrossRefGoogle Scholar
  40. McAdams, H. H. and Arkin, A., 1997, Stochastic mechanisms in gene expression, Proc. Natl. Acad. Sci. USA 94:814–819.CrossRefGoogle Scholar
  41. Møller, A. and Swaddle, J., 1997, Asymmetry, Developmental Stability, and Evolution, Oxford University Press, Oxford.Google Scholar
  42. Neville, A., 1976, Animal Asymmetry, Edward Arnold, London.Google Scholar
  43. O’Grady, K. F. and Antonyshyn, O. M., 1999, Facial asymmetry: Three-dimensional analysis using laser scanning, Plast. Reconstr. Surg. 104:928–940.Google Scholar
  44. Palmer, A., 1994, Fluctuating asymmetry: A primer, in: Developmental Instability: Its Origins and Implications, T. Markow, ed., The Netherlands, Kluwer, Dordrecht, pp. 335–364.Google Scholar
  45. Palmer, A. R., 1996, From symmetry to asymmetry: Phylogenetic patterns of asymmetry variation in animals and their evolutionary significance, Proc. Natl. Acad. Sci. USA 93:14279–14286.CrossRefGoogle Scholar
  46. Palmer, A. and Strobeck, C., 1986, Fluctuating asymmetry: Measurement, analysis, patterns, Ann. Rev. Ecol. Syst. 17:391–421.CrossRefGoogle Scholar
  47. Palmer, A. and Strobeck, C., 1992, Fluctuating asymmetry as a measure of developmental stability: Implications of non-normal distributions and power of statistical tests, Acta Zool. Fenn 191:57–72.Google Scholar
  48. Polak, M., 2003, Developmental Instability: Causes and Consequences, Oxford University Press, Oxford.Google Scholar
  49. Pritchard, M. A. and Kola, I., 1999, The “gene dosage effect” hypothesis versus the “amplified developmental instability” hypothesis in Down syndrome, J. Neural Transm. Suppl. 57:293–303.Google Scholar
  50. Reeves, R., Irving, N., Moran, T., Wohn, A., Kitt, C., Sisodia, S. et al., 1995, A mouse model for Down syndrome exhibits learning and behavior deficits, Nat. Genet. 11:177–184.CrossRefGoogle Scholar
  51. Reeves, R. H., Baxter, L. L., and Richtsmeier, J. T., 2001, Too much of a good thing: Mechanisms of gene action in Down syndrome, Trends Genet. 17:83–88.CrossRefGoogle Scholar
  52. Richtsmeier, J., Cheverud, J., and Lele, S., 1992, Advances in anthropological morphometrics, Ann. Rev. Anthropol. 21:231–253.CrossRefGoogle Scholar
  53. Richtsmeier, J. T., Paik, C. H., Elfert, P. C., Cole, T. M., and Dahlman, H. R., 1995, Precision, repeatability, and validation of the localization of cranial landmarks using computed tomography scans, Cleft Palate Craniofac. J. 32:217–227.CrossRefGoogle Scholar
  54. Richtsmeier, J. T., Baxter, L. L., and Reeves, R. H., 2000, Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice, Dev. Dyn. 217:137–145.CrossRefGoogle Scholar
  55. Richtsmeier, J., DeLeon, V., and Lele, S., 2002a, The promise of geometric morphometrics, Yearb. Phys. Anthropol. 45:63–91.CrossRefGoogle Scholar
  56. Richtsmeier, J. T., Zumwalt, A., Carlson, E. J., Epstein, C. J., and Reeves, R. H., 2002b, Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome, Am. J. Med. Genet. 107:317–324.CrossRefGoogle Scholar
  57. Richtsmeier, J., Leszl, J., Hill, C., Aldridge, K., Aquino, V. et al., 2002c, Development of skull dysmorphology in Ts65Dn segmentally trisomic mice, Am. J. Hum. Genet. Suppl. 72:280 (abstract).Google Scholar
  58. Richtsmeier, J. T., T. M. Cole III, Leszl, J. M., Hill, C. A., Budd, J. L., and Reeves, R. H., 2003, Developmental instability of the skull in aneuploidy, European Society for Evolutionary Biology, 9th Congress, Leeds, August (abstract).Google Scholar
  59. Roche, A., 1964, Skeletal maturation rates in mongolism, Am. J. Roentgenol. 91:979–987.Google Scholar
  60. Roche, A., 1965, The stature of mongols, J. Ment. Defic. Res. 9:131–145.Google Scholar
  61. Rohlf, F. J. and Slice, D. E., 1990, Extensions of the procrustes method for the optimal superimposition of landmarks, Syst. Zool. 39:40–59.CrossRefGoogle Scholar
  62. Sago, H., Carlson, E., Smith, D., Kilbridge, J., Rubin, E., Mobley, W. et al., 1998, Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities, Proc. Natl. Acad. Sci. USA 95:6256–6261.CrossRefGoogle Scholar
  63. Sago, H., Carlson, E., Smith, D. J., Rubin, E. M., Crnic, L. S., Huang, T. T. et al., 2000, Genetic dissection of region associated with behavioral abnormalities in mouse models for Down syndrome, Pediatr. Res. 48:606–613.Google Scholar
  64. Saran, N. G., Pletcher, M. T., Natale, J. E., Cheng, Y., and Reeves, R. H., 2003, Global disruption of the cerebellar transcriptome in a Down syndrome mouse model, Hum. Mol. Genet. 12(16):2013–2019.CrossRefGoogle Scholar
  65. Shapiro, B., 1970, Prenatal dental anomalies in mongolism: Comments on the basis and implications of variability, Ann. NY Acad. Sci. 171:562–577.Google Scholar
  66. Shapiro, B., 1975, Amplified developmental instability in Down syndrome, Ann. Hum. Genet. 38:429–437.Google Scholar
  67. Shapiro, B., 1983, Down syndrome—a disruption of homeostasis, Am. J. Med. Genet. 14:241–269.CrossRefGoogle Scholar
  68. Shapiro, B. L., 1999, The Down syndrome critical region, J. Neural. Transm. Suppl. 57:41–60.Google Scholar
  69. Shapiro, B. L., 2001, Developmental instability of the cerebellum and its relevance to Down syndrome, J. Neural Transm. Suppl. 61 11–34.Google Scholar
  70. Siegel, A. and Benson, R., 1982, A robust comparison of biological shapes, Biometrics 38:341–350.Google Scholar
  71. Smith, D., Crespi, B., and Bookstein, F., 1997, Fluctuating asymmetry in the honey bee, Apis mellifera: Effects of ploidy and hybridzation, J. Evol. Biol. 10:551–574.CrossRefGoogle Scholar
  72. Van Valen, L., 1962, A study of fluctuating asymmetry, Evolution 16:125–142.CrossRefGoogle Scholar
  73. Wagner, G., 1995, Adaptation and the modular design of organisms, in: Advances in Artificial Life, A. Moran, J. Merelo, and P. Chacon, eds., Springer-Verlag, Berlin, pp. 317–328.Google Scholar
  74. Walker, J., 2001, Ability of geometric morphometric methods to estimate a known covariance matrix, Syst. Biol. 49:686–696.CrossRefGoogle Scholar
  75. Zakharov, V., 1992, Population phenogenetics: Analysis of developmental stability in natural populations, Acta Zool. Fenn 191:7–30.Google Scholar

Copyright information

© Kluwer Academic / Plenum Publishers, New York 2005

Authors and Affiliations

  • Joan T. Richtsmeier
    • 1
    • 2
  • Theodore M. ColeIII
    • 3
  • Subhash R. Lele
    • 4
  1. 1.Department of AnthropologyThe Pennsylvania State UniversityUniversity Park
  2. 2.Center for Craniofacial Development and DisordersThe Johns Hopkins UniversityBaltimore
  3. 3.Department of Basic Medical Science, School of MedicineUniversity of Missouri—Kansas CityKansas City
  4. 4.Department of Mathematical and Statistical SciencesUniversity of AlbertaEdmontonCanada

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