Msx2、SLUG、HOXD4基因和神经管畸形关系的初步研究
发布时间：2018-08-31 11:04
【摘要】： 目的 研究山西省汉族人群Msx2A59G、Msx2C386T和SLUGC1548A基因突变状况及其与神经管畸形发病的关系;应用全基因组表达芯片研究山西吕梁地区神经管畸形(neural tube defects, NTDs)胚胎脑组织中特异性表达基因;将差异表达基因从四氢叶酸代谢水平、基因表达调控蛋白、信号转导、凋亡等途径分类;进一步研究与神经系统发育相关的同源异型盒基因HOXD4在神经管畸形疾病中的作用机制。 方法 采用扩增阻碍突变系统法检测Msx2基因A59G位点突变及Msx2基因C386T位点突变和SLUG基因C1548A位点突变;利用全基因组表达芯片高通量筛选出NTDs各发病阶段的异常表达基因;并从生化与分子生物学的角度加以归类,揭示出NTDs的异常基因表达谱;从中选择出HOXD4基因应用半定量RT-PCR技术扩增HOXD4基因并验证其改变。 结果 Logistic回归分析显示:C386T位点T等位基因,C1548A位点A等位基因均与神经管畸形发病有关(P 0.05), C386T位点T等位基因的比值比(OR)为2.756 (95%CI 1.269-5.978)和C1548A位点A等位基因的比值比(OR)为3.610(95%Cl 1.547-8.425);芯片结果显示出异常表达的基因转录本22209个,其中2倍表达增高的基因74个,2倍表达降低的387个,HOXD4基因呈20.9倍增高;半定量RT-PCR结果显示NTDs胚胎中HOXD4基因表达高于对照组(p0.01)。 结论 山西省汉族人群存在Msx2A59G、Msx2C386T和SLUGC1548A基因位点突变。山西省汉族人群Msx2C386T和SLUGC1548A基因位点突变与神经管畸形发病有关,上述两个基因位点突变可能是神经管畸形发病的遗传因素;证明NTDs的发生和发展是多种相关基因表达失常所致,涉及核酸代谢、信号转导、基因表达调控、凋亡等基因的异常改变;证明同源异型盒基因HOXD4在神经系统发育过程中及神经管畸形的病理过程中发挥作用。
[Abstract]:Objective to study the mutation status of Msx2A59G,Msx2C386T and SLUGC1548A genes in Shanxi Han population and its relationship with the pathogenesis of neural tube defects. Using the whole genome expression chip to study the specific expression genes in the brain of (neural tube defects, NTDs) embryos with neural tube malformation in Lv Liang area of Shanxi Province, the differential expression genes were expressed from the level of tetrahydrofolic acid metabolism, gene expression regulatory protein, signal transduction. To further study the mechanism of homologous box gene HOXD4 related to the development of nervous system in neural tube malformation disease. Methods A59G mutation of Msx2 gene, C386T mutation of Msx2 gene and C1548A mutation of SLUG gene were detected by amplification blocking mutation system. The abnormal expression genes of NTDs were screened by high throughput genomic expression microarray and classified from biochemical and molecular biology to reveal the abnormal gene expression profile of NTDs. The HOXD4 gene was selected to amplify the HOXD4 gene by semi-quantitative RT-PCR and to verify its change. Results the Logistic regression analysis showed that the T alleles of C386T locus and C1548A alleles were all related to the pathogenesis of NTM (P0. 05), and the ratio of T alleles at C386T locus to that at C386T locus. The ratio of (OR) to (OR) was 2.756 (95%CI 1.269-5.978) and 3.610 (95%Cl 1.547-8.425) respectively. The expression of HOXD4 gene in NTDs embryos was higher than that in the control group (p0.01), and the expression of HOXD4 gene was 20.9 times higher than that of the control group (p0.01), and the expression of HOXD4 gene in NTDs embryos was significantly higher than that in the control group (p0.01). Conclusion there are Msx2A59G,Msx2C386T and SLUGC1548A loci mutation in Shanxi Han population. The mutation of Msx2C386T and SLUGC1548A gene loci is related to the pathogenesis of neural tube malformation, which may be a genetic factor in the pathogenesis of neural tube malformation, which proves that the occurrence and development of NTDs is caused by the abnormal expression of many related genes. The abnormal changes of genes such as nucleic acid metabolism, signal transduction, gene expression regulation, apoptosis and so on. It is proved that homologous cassette gene HOXD4 plays an important role in the development of nervous system and the pathological process of neural tube malformation.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R394
本文编号：2214790
[Abstract]:Objective to study the mutation status of Msx2A59G,Msx2C386T and SLUGC1548A genes in Shanxi Han population and its relationship with the pathogenesis of neural tube defects. Using the whole genome expression chip to study the specific expression genes in the brain of (neural tube defects, NTDs) embryos with neural tube malformation in Lv Liang area of Shanxi Province, the differential expression genes were expressed from the level of tetrahydrofolic acid metabolism, gene expression regulatory protein, signal transduction. To further study the mechanism of homologous box gene HOXD4 related to the development of nervous system in neural tube malformation disease. Methods A59G mutation of Msx2 gene, C386T mutation of Msx2 gene and C1548A mutation of SLUG gene were detected by amplification blocking mutation system. The abnormal expression genes of NTDs were screened by high throughput genomic expression microarray and classified from biochemical and molecular biology to reveal the abnormal gene expression profile of NTDs. The HOXD4 gene was selected to amplify the HOXD4 gene by semi-quantitative RT-PCR and to verify its change. Results the Logistic regression analysis showed that the T alleles of C386T locus and C1548A alleles were all related to the pathogenesis of NTM (P0. 05), and the ratio of T alleles at C386T locus to that at C386T locus. The ratio of (OR) to (OR) was 2.756 (95%CI 1.269-5.978) and 3.610 (95%Cl 1.547-8.425) respectively. The expression of HOXD4 gene in NTDs embryos was higher than that in the control group (p0.01), and the expression of HOXD4 gene was 20.9 times higher than that of the control group (p0.01), and the expression of HOXD4 gene in NTDs embryos was significantly higher than that in the control group (p0.01). Conclusion there are Msx2A59G,Msx2C386T and SLUGC1548A loci mutation in Shanxi Han population. The mutation of Msx2C386T and SLUGC1548A gene loci is related to the pathogenesis of neural tube malformation, which may be a genetic factor in the pathogenesis of neural tube malformation, which proves that the occurrence and development of NTDs is caused by the abnormal expression of many related genes. The abnormal changes of genes such as nucleic acid metabolism, signal transduction, gene expression regulation, apoptosis and so on. It is proved that homologous cassette gene HOXD4 plays an important role in the development of nervous system and the pathological process of neural tube malformation.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R394
【参考文献】
相关期刊论文 前3条
1 毛东伟,李守柔;Cx43、同型半胱氨酸及Pax3与神经管缺陷畸形[J];国外医学(妇幼保健分册);2001年01期
2 赵如冰;胱硫脒-β-合成酶及其与神经管畸形的关系[J];国外医学.妇幼保健分册;1998年01期
3 裴丽君,李竹,李松,洪世欣,叶荣伟,陈新,郑俊池,王太梅,赵秀琴,肖岚,王丽娜,张伯兰,刘志欣,周永兰,姜梅芳,孙霞美,陈海兰,李敏,杨晓玲,沈泉珍,邵佩云,谢连云;中国神经管畸形高低发地区季节及性别分布特征[J];中华流行病学杂志;2003年06期
，本文编号：2214790
本文链接：https://www.wllwen.com/yixuelunwen/binglixuelunwen/2214790.html
最近更新
教材专著
