Conclusion: Trends and Predictions for Genetic and Developmental Biological Research on Scoliosis

  • Kenro Kusumi


Developmental and genetic studies of the spine, genetic linkage to vertebral anomalies, and family-based association studies have led to advances in understanding the genetic causes of idiopathic and congenital scoliosis. Chapters in this volume have been prepared by research leaders who have been working to identify the genetic and developmental causes of idiopathic and congenital scoliosis. Technological advances in high-throughput sequencing, genotyping, bioinformatics, and medical imaging continue to push forward the limit of possible advances in scoliosis research. Combined with changes in the scale of human genetics research, we anticipate that the next decade could see an exponential increase in the number of genes associated with congenital and idiopathic scoliosis, and a greater understanding of the developmental mechanisms underlying “idiopathic” scoliosis.


Idiopathic Scoliosis Cell Culture Model Spinal Curvature Congenital Scoliosis Spinal Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Collins, F.S., Finnell, R.H., Rossant, J., and Wurst, W. 2007. A new partner for the International knockout mouse consortium. Cell 129(2):235.CrossRefPubMedGoogle Scholar
  2. Dequéant, M.L., Glynn, E., Gaudenz, K., Wahl, M., Chen, J., Mushegian, A., and Pourquié, O. 2006. A complex oscillating network of signaling genes underlies the mouse segmentation clock. Science 314:1595–1598.CrossRefPubMedGoogle Scholar
  3. Evangelou, E., Chapman, K., Meulenbelt, I., Karassa, F.B., Loughlin, J., Carr, A., Doherty, M., Doherty, S., Gómez-Reino, J.J., Gonzalez, A. et al. 2009. Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand. Arthritis Rheum. 60(6):1710–1721.CrossRefPubMedGoogle Scholar
  4. Gorman, K.F., Tredwell, S.J., Breden, F. 2007. The mutant guppy syndrome curveback as a model for human heritable spinal curvature. Spine 32(7):735–741.CrossRefPubMedGoogle Scholar
  5. Gudbjartsson, D.F., Bjornsdottir, U.S., Halapi, E., Helgadottir, A., Sulem, P., Jonsdottir, G.M., Thorleifsson, G., Helgadottir, H., Steinthorsdottir, V., Stefansson, H. et al. 2009. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet. 41(3):342–347.CrossRefPubMedGoogle Scholar
  6. Gudmundsson, J., Sulem, P., Gudbjartsson, D.F., Jonasson, J.G., Sigurdsson, A., Bergthorsson, J.T., He, H., Blondal, T., Geller, F., Jakobsdottir, M. et al. 2009. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat. Genet. 41(4):460–464.CrossRefPubMedGoogle Scholar
  7. Hirata, H., Bessho, Y., Kokubu, H., Masamizu, Y., Yamada, S., Lewis, J., and Kageyama, R. 2004. Instability of Hes7 protein is crucial for the somite segmentation clock. Nat. Genet. 36:750–754.CrossRefPubMedGoogle Scholar
  8. International Human Genome Sequencing Consortium. 2004. Finishing the euchromatic sequence of the human genome. Nature 431(7011):931–945.CrossRefGoogle Scholar
  9. Lewis, J. 2003. Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator. Curr. Biol. 13(16):1398–1408.CrossRefPubMedGoogle Scholar
  10. Lindgren, C.M., Heid, I.M., Randall, J.C., Lamina, C., Steinthorsdottir, V., Qi, L., Speliotes, E.K., Thorleifsson, G., Willer, C.J., Herrera, B.M. et al. 2009. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution. PLoS Genet. 5(6):e1000508.CrossRefPubMedGoogle Scholar
  11. Loomes, K.M., Stevens, S.A., O‘Brien, M.L., Gonzalez, D.M., Ryan, M.J., Segalov, M., Dormans, N.J., Mimoto, M.S., Gibson, J.D., Sewell, W., Schaffer, A.A., Nah, H.D., Rappaport, E.F., Pratt, S.C., Dunwoodie, S.L., and Kusumi, K. 2007. Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects. Dev. Dyn. 236:2943–2951.CrossRefPubMedGoogle Scholar
  12. Machka, C., Kersten, M., Zobawa, M., Harder, A., Horsch, M., Halder, T., Lottspeich, F., Hrabĕ de Angelis, M., and Beckers, J. 2005. Identification of Dll1 (Delta1) target genes during mouse embryogenesis using differential expression profiling. Gene Expr. Patterns 6:94–101.CrossRefPubMedGoogle Scholar
  13. Monk, N.A.M. 2003. Oscillatory expression of Hes1, p53 and NF-kB driven by transcriptional time delays. Curr. Biol. 13:1409–1413.CrossRefPubMedGoogle Scholar
  14. Niwa, Y., Masamizu, Y., Liu, T., Nakayama, R., Deng, C.X., and Kageyama, R. 2007. The initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and notch signaling in the somite segmentation clock. Dev. Cell. 13:298–304.CrossRefPubMedGoogle Scholar
  15. Price, A.L., Helgason, A., Palsson, S., Stefansson, H., St Clair, D., Andreassen, O.A., Reich, D., Kong, A., and Stefansson, K. 2009. The impact of divergence time on the nature of population structure: an example from Iceland. PLoS Genet. 5(6):e1000505.CrossRefGoogle Scholar
  16. Rujescu, D., Ingason, A., Cichon, S., Pietiläinen, O.P., Barnes, M.R., Toulopoulou, T., Picchioni, M., Vassos, E., Ettinger, U., Bramon, E. et al. 2009. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum. Mol. Genet. 18(5):988–996.PubMedGoogle Scholar
  17. Thorleifsson, G., Holm, H., Edvardsson, V., Walters, G.B., Styrkarsdottir, U., Gudbjartsson, D.F., Sulem, P., Halldorsson, B.V., de Vegt, F., d‘Ancona, F.C. et al. 2009. Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density. Nat. Genet. Jun 28 Epub ahead of print.Google Scholar
  18. Sewell, W., Sparrow, D., Gonzalez, D.M., Smith, A., Eckalbar, W., Gibson, J., Dunwoodie, S.L., and Kusumi, K. 2009. Cyclical expression of the Notch/Wnt regulator Nrarp requires Dll3 function in somitogenesis. Dev. Biol. 329:400–409.CrossRefPubMedGoogle Scholar
  19. Turner, D.J., Keane, T.M., Sudbery, I., and Adams, D.J. 2009. Next-generation sequencing of vertebrate experimental organisms. Mamm. Genome. 20:327–338.CrossRefPubMedGoogle Scholar
  20. Wardle, F.C. and Papaioannou, V.E. 2008. Teasing out T-box targets in early mesoderm. Curr. Opin. Genet. Dev. 18:418–425.Google Scholar
  21. William, D.A., Saitta, B., Gibson, J.D., Traas, J., Markov, V., Gonzalez, D.M., Sewell, W., Anderson, D.M., Pratt, S.C., Rappaport, E.F., and Kusumi, K. 2007. Identification of oscillatory genes in somitogenesis from functional genomic analysis of a human mesenchymal stem cell model. Dev. Biol. 305:172–186.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.School of Life Sciences, Arizona State UniversityTempeUSA
  2. 2.Department of Basic Medical SciencesThe University of Arizona College of Medicine–Phoenix in Partnership with Arizona State UniversityPhoenixUSA

Personalised recommendations