Idiopathic Scoliosis Families Highlight Actin-Based and Microtubule-Based Cellular Projections and Extracellular Matrix in Disease Etiology

G3: Genes, Genomes, Genetics

article

Erin E. Baschal¹  Elizabeth A. Terhune¹  Cambria I. Wethey¹  Robin M. Baschal¹  Kandice D. Robinson¹  Melissa T. Cuevas¹  Shreyash Pradhan¹  Brittan S. Sutphin¹  Matthew R. G. Taylor³  Katherine Gowan⁴  Chad G. Pearson⁵  Lee A. Niswander⁴  Kenneth L. Jones⁴  Nancy H. Miller¹ 

[1] Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO;Musculoskeletal Research Center, Children’s Hospital Colorado, Aurora, CO;Department of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO;Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO;Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO;Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO

关键词: Keywords: idiopathic scoliosis;    exome sequencing;    actin cytoskeleton;    microtubules;    cilia;    extracellular matrix;   

DOI  :  10.1534/g3.118.200290

学科分类：社会科学、人文和艺术（综合）

来源: Genetics Society of America

【 摘 要 】

Idiopathic scoliosis (IS) is a structural lateral spinal curvature of ≥10° that affects up to 3% of otherwise healthy children and can lead to life-long problems in severe cases. It is well-established that IS is a genetic disorder. Previous studies have identified genes that may contribute to the IS phenotype, but the overall genetic etiology of IS is not well understood. We used exome sequencing to study five multigenerational families with IS. Bioinformatic analyses identified unique and low frequency variants (minor allele frequency ≤5%) that were present in all sequenced members of the family. Across the five families, we identified a total of 270 variants with predicted functional consequences in 246 genes, and found that eight genes were shared by two families. We performed GO term enrichment analyses, with the hypothesis that certain functional annotations or pathways would be enriched in the 246 genes identified in our IS families. Using three complementary programs to complete these analyses, we identified enriched categories that include stereocilia and other actin-based cellular projections, cilia and other microtubule-based cellular projections, and the extracellular matrix (ECM). Our results suggest that there are multiple paths to IS and provide a foundation for future studies of IS pathogenesis.

【 授权许可】

CC BY|CC BY-NC