随着我国社会发展和人民生活水平的提高,人类疾病谱发生了结构性的改变,遗传性疾病和出生缺陷发生比例逐年增高。据统计,我国人口中约有1/51/4患者有各种遗传病或与遗传有关的疾病。当前我国出生缺陷的发生率为4%6%,每年约有80100万缺陷儿童出生,给社会和家庭带来巨大负担。人们对于遗传咨询、遗传诊断和产前诊断及其它临床遗传服务的需求与日俱增。

临床遗传学面临的主要问题是遗传病与出生缺陷的成因复杂,涉及环境、遗传、表观遗传、营养、行为、母体内分泌和代谢等多方面因素,致畸因素的作用机制以及互作关系尚待深入解析。本研究方向拟针对遗传病、生殖健康和出生缺陷的关键核心科学问题进行研究,即主要的遗传变异,遗传变异及不良环境等协同发挥致畸作用的方式,选择采用有效集成方式针对关键病因和发病环节进行有效的人群干预。研究内容包括:

1、与临床医院合作,按照知情同意的原则,建立规范的调查登记表和相关样本采集流程,通过采集北方地区常见的严重遗传病与出生缺陷患者、家系个体及对照人群队列的血液(及组织样本),收集临床资料包括生化指标、影像学数据等,建立中国北方遗传病与出生缺陷遗传资源库。

2、采用全基因组测序、全外显子组测序、Array-CGHFISH 及生物信息学等方法,筛选鉴定出新的遗传病及出生缺陷致病基因和致病性遗传变异及表观遗传学变异并在患者和人群队列中进行验证。

3、鉴定疾病发生的易感、致病位点,揭示遗传病与出生缺陷发生的遗传机制。

4、构建不同的致病基因或遗传变异出生缺陷动物模型,探究遗传因素异常导致出生缺陷的致病机制。

5、以此建立北方常见严重遗传病和出生缺陷的研究技术路线和方法,并通过一系列研究建立“中国人群出生缺陷致病遗传变异数据库”。

发表学术文章(*通讯作者)

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2.  Jia X, Zhang F, Bai J, Gao L, Zhang X, Sun H, Sun D, Guan R, Sun W, Xu L, Yue Z, Yu Y, Fu S*. (2013)Combinational analysis of linkage and exome sequencing identifies the causative mutation in a Chinese family with congenital cataract.BMC Med Genet. 14:107. PMID:  24103489

3.        Zhang X, Qiao H, Zhao Y, Wang X, Sun H, Liu A, Xu L, Sun D, Jin Y, Yu Y, Meng X, Bai J, Chen F, Fu S*. (2012) Association of single nucleotide polymorphisms in TCF2 with type 2 diabetes susceptibility in a Han Chinese population. PLoS One. 7(12): e52938. PMID: 3534126

4.        Zhou J, Sun D, Xu L, Sun L, Fu S, Li Y*. (2011) ADAM33 as a psoriasis susceptibility gene in the Han population of northeastern China. Dermatology. 223(4):356-62. PMID: 22269827

5.        Qiao H, Zhang X, Zhao X, Zhao Y, Xu L, Sun H, Fu S*. (2012) Genetic variants of TCF7L2 are associated with type 2 diabetes in a northeastern Chinese population. Gene. 495(2):115-9. PMID: 22245614

6.        Han D, Shen C, Meng X, Bai J, Chen F, Yu Y, Jin Y, Fu S*. (2012) Methionine synthase reductase A66G polymorphism contributes to tumor susceptibility: evidence from 35 case-control studies. Mol Biol Rep. 39(2):805-16. PMID: 21547363

7.        Sun H, Bai J, Chen F, Jin Y, Yu Y, Fu S*. (2011) Lack of an association between AURKA T91A polymorphisms and breast cancer: a meta-analysis involving 32,141 subjects. Breast Cancer Res Treat. 125(1):175-9. PMID: 20464476

8.        Sun H, Bai J, Chen F, Jin Y, Yu Y, Jin L, Fu S*. (2011) RAD51 G135C polymorphism is associated with breast cancer susceptibility: a meta-analysis involving 22,399 subjects. Breast Cancer Res Treat. 125(1):157-61. PMID: 20454923

9.        Shen C, Sun H, Sun D, Xu L, Zhang X, Liu A, Jia X, Bai J, Chen F, Yu Y, Jin Y, Yu J, Fu S*. (2011) Polymorphisms of tumor necrosis factor-alpha and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 126(3):763-70. PMID: 20882404

10.        Sun H, Qiao Y, Zhang X, Xu L, Jia X, Sun D, Shen C, Liu A, Zhao Y, Jin Y, Yu Y, Bai J, Fu S*. (2010) XRCC3 Thr241Met polymorphism with lung caner and bladder cancer: A meta-analysis. Cancer Sci. 101(8):1777-82. PMID: 20500515

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12.    Wu J, Ren X, Zhang X, Li C, Li Y, Ma H, Zhou Y, Jin Y, Chen F, Bai J, Fu S*. (2010) The vascular endothelial growth factor +405 G/C polymorphism in psoriasis. J Dermatol Sci. 57(1):62-3. PMID: 19931423

13.    Xu L, Qiao Y, Zhang X, Sun H, Wang J, Sun D, Jia X, Shen C, Zhao Y, Jin Y, Yu Y, Ling H, Wang K, Fu S*. (2011) A haplotype in the CCR5 gene promoter was associated with the susceptibility to HIV-1 infection in a northern Chinese population. Mol Biol Rep. 38(1):327-32. PMID: 20364409

14.    Xu Z, Sun H, Yu Y, Jin Y, Meng X, Sun D, Bai J, Chen F, Fu S*. (2010) Diversity of five novel Y-STR loci and their application in studies of north Chinese populations. J Genet. 89(1):29-36. PMID: 20505244

15.    Jiang J, Zhang X, Sun D, Jin Y, Bai J, Chen F, Fu S*. (2010) Study on VNTR polymorphism of gene IL-1RA in 19 Chinese populations. Int J Immunogenet. 37(2):73-7. PMID: 20002810

16.    Xu L, Qiao Y, Zhang X, Sun H, Wang J, Sun D, Jin Y, Yu Y, Chen F, Bai J, Ling H, Wang K, Fu S*. (2010) CCR2-64I allele is associated with the progression of AIDS in a Han Chinese population. Mol Biol Rep. 37(1):311-6. PMID: 19669591

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