Whole-genome sequencing reveals novel genes in ossification of the posterior longitudinal ligament of the thoracic spine in the Chinese population

J Orthop Surg Res. 2018 Dec 22;13(1):324. doi: 10.1186/s13018-018-1022-8.

Abstract

Background: Ossification of the posterior longitudinal ligament (OPLL) of the spine is a complex, multifactorial disease. Although several genes that are linked to cervical OPLL susceptibility have been reported, specific genetic studies regarding thoracic OPLL are lacking. Whole-genome sequencing has been considered as an efficient strategy to search for disease-causing genes.

Methods: We analysed whole-genome sequences in a cohort of 25 unrelated patients with thoracic OPLL. Bioinformatics analysis and various algorithms were used to predict deleterious variants. Sanger sequencing was used to confirm the variants.

Results: Four deleterious mutations in three genes (c.2716C>T (p.Arg906Cys) in collagen type VI α6 (COL6A6); c.1946G>C (p.Gly649Ala) in collagen type IX α1 (COL9A1); and c.301T>C (p.Ser101Pro) and c.171A>G (p.Ile57Met) in toll-like receptor 1 (TLR1)) were successfully identified. All the variants were confirmed by Sanger sequencing.

Conclusion: The novel deleterious mutations of the three genes may contribute to the development of thoracic OPLL.

Keywords: Ossification of the posterior longitudinal ligament; Susceptible gene; Thoracic; Whole-genome sequencing.

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics*
  • Collagen Type IX / genetics
  • Collagen Type VI / genetics
  • Computational Biology / methods
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Ossification of Posterior Longitudinal Ligament / genetics*
  • Thoracic Vertebrae
  • Toll-Like Receptor 1 / genetics
  • Whole Genome Sequencing / methods

Substances

  • COL6A6 protein, human
  • COL9A1 protein, human
  • Collagen Type IX
  • Collagen Type VI
  • TLR1 protein, human
  • Toll-Like Receptor 1