28 / 2017-05-05 15:08:21

Identification of susceptibility loci for thoracic ossification of the posterior longitudinal ligament by whole-genome sequencing

thoracic ossification of posterior longitudinal ligament,412,whole genome sequencing

Objective: To identify genetic factors for thoracic ossification of the posterior longitudinal ligament(T-OPLL) by performing whole-genome sequencing (WGS) in 30 unrelated northern Chinese Han patients with T-OPLL,to determine the association of genetic defects and T-OPLL.
Methods:Peripheral blood was collected and genomic DNA was isolated from 30 patients. we performed WGS of 30 DNA samples on Illumina HiSeq Xten sequencer. Potential deleterious effects of identified sequence variants were assessed by bioinformatics analysis and various algorithms.Selected variants were further validated by Sanger sequencing and ELISA.
Results: Two deleterious variants, i.e., c.1534G>A(p.Gly512Ser)/COL6A1 and c.2275C>A(p.Leu759Ile)/IL17RC, were identified in seven unrelated patients. Furthermore, these two mutations resulted in markedly increased gene expression levels in peripheral blood samples.
Conclusion: We identified two new potential pathogenic loci in Han Chinese patients with T-OPLL, for the first time, using WGS. The results of the current study provide insights into the molecular aetiology of OPLL.