Targeted next-generation sequencing reveals multiple deleterious variants in OPLL-associated genes

Scientific Reports
Xin ChenJie Du


Ossification of the posterior longitudinal ligament of the spine (OPLL), which is characterized by ectopic bone formation in the spinal ligaments, can cause spinal-cord compression. To date, at least 11 susceptibility genes have been genetically linked to OPLL. In order to identify potential deleterious alleles in these OPLL-associated genes, we designed a capture array encompassing all coding regions of the target genes for next-generation sequencing (NGS) in a cohort of 55 unrelated patients with OPLL. By bioinformatics analyses, we successfully identified three novel and five extremely rare variants (MAF < 0.005). These variants were predicted to be deleterious by commonly used various algorithms, thereby resulting in missense mutations in four OPLL-associated genes (i.e., COL6A1, COL11A2, FGFR1, and BMP2). Furthermore, potential effects of the patient with p.Q89E of BMP2 were confirmed by a markedly increased BMP2 level in peripheral blood samples. Notably, seven of the variants were found to be associated with the patients with continuous subtype changes by cervical spinal radiological analyses. Taken together, our findings revealed for the first time that deleterious coding variants of the four OPLL-associated genes are p...Continue Reading


Jul 12, 2019·Journal of Orthopaedic Surgery and Research·Peng WangShibao Lu
Mar 14, 2019·International Journal of Molecular Medicine·Peng WangShibao Lu


Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·E A WangJ M Wozney
Jun 19, 1998·American Journal of Human Genetics·H KogaM Leppert
Aug 10, 2000·The Journal of Biological Chemistry·Y Zhang, Q Chen
May 9, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·S MaedaI Inoue
Jan 5, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kozo FurushimaIturo Inoue
Apr 5, 2008·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Hao WangXin Lin
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng Li1000 Genome Project Data Processing Subgroup
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Dec 15, 2010·PLoS Computational Biology·Eugene V DavydovSerafim Batzoglou
Mar 15, 2011·Oncotarget·Jian HeNickolas Papadopoulos
Jul 22, 2011·Science Translational Medicine·Jian WuBert Vogelstein
Dec 17, 2011·Science Translational Medicine·Ai-Luen WuJunichiro Sonoda
Jun 13, 2012·Nucleic Acids Research·Ngak-Leng SimPauline C Ng
Dec 12, 2012·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Dong Wook JekarlChoon Ho Sung
Apr 10, 2013·Human Mutation·Birgit Sikkema-RaddatzRichard J Sinke
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow
Dec 17, 2014·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Shiro Ikegawa

Related Concepts

Fibroblast Growth Factor Receptor 1
Peripheral Blood
Procollagen Type VI
Pathogenic Organism
FGFR1 wt Allele
BMP2 gene
Candidate Disease Gene

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.