Whole-genome sequencing reveals novel genes in ossification of the posterior longitudinal ligament of the thoracic spine in the Chinese population
Whole-genome sequencing reveals novel genes in ossification of the posterior longitudinal ligament of the thoracic spine in the Chinese population
复制标题
全基因组测序揭示中国人群胸椎后纵韧带骨化的新基因
DOI：
10.1186/s13018-018-1022-8
复制
发表时间：
2018-12-22
影响因子：
2.6
通讯作者：
Liu, Zhongjun
中科院分区：
文献类型：
--
作者：
Liang, Chen;Wang, Peng;Liu, Zhongjun
脊柱后纵韧带骨化是一种复杂、多因素的疾病。虽然已经报道了几个与颈部OPLL易感性有关的基因，但关于胸部OPLL的特定遗传学研究尚缺乏。全基因组测序一直被认为是寻找致病基因的有效策略。方法我们分析了25例无亲缘关系的胸部OPLL患者的全基因组序列。生物信息学分析和各种算法被用来预测有害的变异。结果在VI型胶原基因(COL6A6)的c.2716C和gt；T(p.Arg906Cys)；在IX型胶原(COL9A1)的c.1946G和gt；C(p.Gly649Ala)；在Toll样受体1(TLR1)的c.301T>；C(p.Ser101Pro)和c.171a>；G(p.Ile57Met)中，成功检测到4个有害突变。结论这三个基因的新的有害突变可能与胸部OPLL的发生有关。
BackgroundOssification 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.MethodsWe 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.ResultsFour deleterious mutations in three genes (c.2716C>T (p.Arg906Cys) in collagen type VI 6 (COL6A6); c.1946G>C (p.Gly649Ala) in collagen type IX 1 (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.ConclusionThe novel deleterious mutations of the three genes may contribute to the development of thoracic OPLL.