【摘要】： 目的 研究山西省漢族人群Msx2A59G、Msx2C386T和SLUGC1548A基因突變狀況及其與神經(jīng)管畸形發(fā)病的關(guān)系;應(yīng)用全基因組表達芯片研究山西呂梁地區(qū)神經(jīng)管畸形(neural tube defects, NTDs)胚胎腦組織中特異性表達基因;將差異表達基因從四氫葉酸代謝水平、基因表達調(diào)控蛋白、信號轉(zhuǎn)導(dǎo)、凋亡等途徑分類;進一步研究與神經(jīng)系統(tǒng)發(fā)育相關(guān)的同源異型盒基因HOXD4在神經(jīng)管畸形疾病中的作用機制。 方法 采用擴增阻礙突變系統(tǒng)法檢測Msx2基因A59G位點突變及Msx2基因C386T位點突變和SLUG基因C1548A位點突變;利用全基因組表達芯片高通量篩選出NTDs各發(fā)病階段的異常表達基因;并從生化與分子生物學(xué)的角度加以歸類,揭示出NTDs的異常基因表達譜;從中選擇出HOXD4基因應(yīng)用半定量RT-PCR技術(shù)擴增HOXD4基因并驗證其改變。 結(jié)果 Logistic回歸分析顯示:C386T位點T等位基因,C1548A位點A等位基因均與神經(jīng)管畸形發(fā)病有關(guān)(P 0.05), C386T位點T等位基因的比值比(OR)為2.756 (95%CI 1.269-5.978)和C1548A位點A等位基因的比值比(OR)為3.610(95%Cl 1.547-8.425);芯片結(jié)果顯示出異常表達的基因轉(zhuǎn)錄本22209個,其中2倍表達增高的基因74個,2倍表達降低的387個,HOXD4基因呈20.9倍增高;半定量RT-PCR結(jié)果顯示NTDs胚胎中HOXD4基因表達高于對照組(p0.01)。 結(jié)論 山西省漢族人群存在Msx2A59G、Msx2C386T和SLUGC1548A基因位點突變。山西省漢族人群Msx2C386T和SLUGC1548A基因位點突變與神經(jīng)管畸形發(fā)病有關(guān),上述兩個基因位點突變可能是神經(jīng)管畸形發(fā)病的遺傳因素;證明NTDs的發(fā)生和發(fā)展是多種相關(guān)基因表達失常所致,涉及核酸代謝、信號轉(zhuǎn)導(dǎo)、基因表達調(diào)控、凋亡等基因的異常改變;證明同源異型盒基因HOXD4在神經(jīng)系統(tǒng)發(fā)育過程中及神經(jīng)管畸形的病理過程中發(fā)揮作用。
[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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：R394

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