Whole-genome methylation analysis reveals novel epigenetic perturbations of congenital scoliosis

Gang Liu; Hengqiang Zhao; Zihui Yan; Sen Zhao; Yuchen Niu; Xiaoxin Li; Shengru Wang; Yang Yang; Sen Liu; Terry Jianguo Zhang; Zhihong Wu; Nan Wu

Molecular Therapy: Nucleic Acids (Mar 2021)

Whole-genome methylation analysis reveals novel epigenetic perturbations of congenital scoliosis

Gang Liu,
Hengqiang Zhao,
Zihui Yan,
Sen Zhao,
Yuchen Niu,
Xiaoxin Li,
Shengru Wang,
Yang Yang,
Sen Liu,
Terry Jianguo Zhang,
Zhihong Wu,
Nan Wu

Affiliations

Gang Liu: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Hengqiang Zhao: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Zihui Yan: Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Sen Zhao: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China
Yuchen Niu: Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Xiaoxin Li: Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
Shengru Wang: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing 100730, China
Yang Yang: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing 100730, China
Sen Liu: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing 100730, China
Terry Jianguo Zhang: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing 100730, China
Zhihong Wu: Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing 100730, China
Nan Wu: Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China; Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing 100730, China; Corresponding author: Nan Wu, Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing 100730, China.

Journal volume & issue: Vol. 23
pp. 1281 – 1287

Abstract

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Congenital scoliosis (CS) is a congenital disease caused by malformations of vertebrae. Recent studies demonstrated that DNA modification could contribute to the pathogenesis of disease. This study aims to identify epigenetic perturbations that may contribute to the pathogenesis of CS. Four CS patients with hemivertebra were enrolled and underwent spine correction operations. DNA was extracted from the hemivertebrae and spinal process collected from the specimen during the hemivertebra resection. Genome-wide DNA methylation profiling was examined at base-pair resolution using whole-genome bisulfite sequencing (WGBS). We identified 343 genes with hyper-differentially methylated regions (DMRs) and 222 genes with hypo-DMRs, respectively. These genes were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, calcium signaling pathway, and axon guidance in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and were enriched in positive regulation of cell morphogenesis involved in differentiation, regulation of cell morphogenesis involved in differentiation, and regulation of neuron projection development in Biological Process of Gene Ontology (GO-BP) terms. Hyper-DMR-related genes, including IGHG1, IGHM, IGHG3, RNF213, and GSE1, and hypo DMR-related genes, including SORCS2, COL5A1, GRID1, RGS3, and ROBO2, may contribute to the pathogenesis of hemivertebra. The aberrant DNA methylation may be associated with the formation of hemivertebra and congenital scoliosis.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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