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Genetics and Functional Pathology of Idiopathic Scoliosis

  • Elizabeth A. Terhune
  • Erin E. Baschal
  • Nancy Hadley Miller
Chapter

Abstract

Idiopathic scoliosis (IS) has been understood to have a familial or genetic component for decades, yet the genetic mechanisms underlying the disorder are still a subject of active investigation. Identification of genes related to this condition has been difficult due to a number of factors, including genetic heterogeneity, phenotypic heterogeneity, and inconsistent exclusion and inclusion criteria for genetic study participants. Discoveries have kept pace with available genetic technologies, with potentially causal genes and regions having been identified by linkage analyses, candidate gene sequencing, genome-wide association studies (GWAS), and next-generation sequencing methods. The genetic associations with IS that have been replicated to date are variants in or near LBX1 and GPR126, as well as rare variants in multiple extracellular matrix genes. Early animal models of IS have included pinealectomized chickens and bipedal rodents, which led to an interest in melatonin signaling dysfunction as a possible cause of IS. Bony fishes have recently emerged as leading models of IS, starting with the curveback mutant guppy line and progressing to the zebrafish, which was more recently used to create a late-onset scoliosis phenotype through mutations in ptk7 and other motile cilia genes. Today, these animal models in combination with modern sequencing technologies provide powerful tools for the IS research community, with immense potential toward the discovery of additional IS candidate genes and pathways. Determining the genetic factors underlying IS may ultimately improve patient care through diagnostic testing and treatments for affected children.

Keywords

Genetics Complex traits Idiopathic scoliosis Animal models Candidate genes Genetic variants 

Notes

Acknowledgments

We thank the laboratory of Dr. Brian Ciruna for providing the micro-CT image of the mutant ptk7 zebrafish in Fig. 7.2.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Elizabeth A. Terhune
    • 1
  • Erin E. Baschal
    • 1
  • Nancy Hadley Miller
    • 1
    • 2
  1. 1.Department of OrthopedicsUniversity of Colorado Anschutz Medical CampusAuroraUSA
  2. 2.Musculoskeletal Research Center, Children’s Hospital ColoradoAuroraUSA

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