先天性脊柱侧凸基于同卵双生双胞胎模型的病因学研究

先天性脊柱侧凸（congenital scoliosis, CS）在新生儿中发病率为0.5-1/1000，其发病机理尚不清楚，但多数学者推测与遗传突变或妊娠时的环境因素有关。CS是一种散发疾病，无法通过基于家系的连锁分析来鉴定与其相关的染色体区域；同时，作为没有前期工作铺垫的复杂疾病，贸然采用GWAS方法分析，其高额的经费投入风险会很高。我们希望能够找到一种新的研究方法，可以低投入并且有效地研究类似CS这种背景不清的先天性复杂疾病。表型存在差异的同卵双胞胎是研究此类疾病的理想模型，他们应该具有一致的DNA序列，但却存在表型以及疾病易感性的差异。通过对其进行全基因组遗传和表观遗传分析，可获取和表型相关的DNA突变和甲基化差异位点信息，从而明确先天性脊柱侧凸的潜在发病机制。集中人力、物力、财力保护这样的病例资源，并探索其相应研究策略，将极大推动CS乃至其他复杂先天疾病的预防、诊断和治疗进程。

he prevalence rate of congenital scoliosis (CS) is thought to be approximately 0.5 to 1 in 1000 live births. There is currently no known cause for the development of a congenital vertebral anomaly. Most scientists suggest that genetic mutation and the environmental affection during pregnancy are possible causes for congenital scoliosis. CS is a sporadic disease, which is hard to be studied by linkage analysis. Meanwhile, it is too risky to perform GWAS on those diseases like CS that there is limited background knowledge of them. We hope to find new research strategies with low-input, which can effectively investigate these complex congenital diseases. Identical twins with different phenotypes are ideal models. We used identical twins as research model, as well as combined with exon capture sequencing and MeDIP-seq technologies, to enclose the genetic and epigenetic features of complex congenital bone disease in genome scale. Concentrate manpower, material and financial resources to protect such valuable identical twins resources, and to explore related research strategies, will greatly promote the prevention, diagnosis and treatment of congenital complex diseases.