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Summary

Elucidation of the genetic basis for heritable spinal curvature would be highly beneficial to medicine. Heritable spinal curvature among otherwise healthy children (i.e. idiopathic-type) accounts for more than 80% of all human spinal curvatures and imposes a substantial healthcare cost through bracing, hospitalizations, surgery, and chronic back pain. Despite the prevalence and impact of heritable spinal curvatures, their genetic architecture and specific genes involved are unknown. With the human idiopathic scoliosis syndrome (IS), the most prevalent idiopathic-type spinal deformity, the current view is that it is a complex genetic disorder with multiple genes segregating in the population, exhibiting complex genotype by environment interactions. With complex human syndromes that involve interactions among genetic, physiological, and environmental factors, an important experimental approach is to identify genes or biochemical compounds in a model animal with a similar phenotype. Spinal curvature is a prevalent deformity among teleosts. We hypothesize that genetic factors related to curvature in teleosts and humans share common biological pathway(s). This is based on the fact that fish and humans share developmental pathways, physiological mechanisms and organ systems, and that comparative genomics has identified conserved DNA sequences and gene networks. The guppy curveback phenotype has been extensively characterized so that the lineage can be applied as a model for understanding the biological context of heritable spinal curvature. The identification of a major quantitative trait locus (QTL) is a first step in understanding the genetics of this type of deformity and will lead to the identification of important pathways associated with spinal integrity. As a model, curveback demonstrates that teleosts are important for understanding not only the basic biology of heritable spinal curvatures, but also the phenotypic variation that is a consequence of genotypic and environmental interactions. Considering that teleost models are highly tractable and have genomic tools available, their application to human orthopaedic study offers an opportunity for greater insight into the biology of vertebral deformity and integrity.