【摘要】：目的：心腦血管病是人類(lèi)健康的最主要威脅之一,高血壓是心腦血管病的最大危險(xiǎn)因素,并已成為我國(guó)沉重社會(huì)負(fù)擔(dān)。因此闡明高血壓的發(fā)生、發(fā)展和轉(zhuǎn)歸規(guī)律仍是高血壓防治的關(guān)鍵。研究表明,高血壓是一種遺傳和環(huán)境因素相互作用的復(fù)雜疾病。候選基因策略和全基因組關(guān)聯(lián)研究獲得的所有易感位點(diǎn)均未顯示出與高血壓的較強(qiáng)關(guān)聯(lián)性,高血壓的病因問(wèn)題仍然沒(méi)有確定解釋。近年來(lái),高血壓表觀遺傳學(xué)研究已經(jīng)找到一些線索,可能在環(huán)境因素與核基因組間起到溝通橋梁作用,在沒(méi)有發(fā)生基因組變異的情況下影響基因表達(dá)水平,從而影響疾病的易感性。DNA甲基化是4個(gè)表觀遺傳調(diào)控的重要方式之一。但是在高血壓領(lǐng)域,DNA甲基化的研究還有很多問(wèn)題亟待解答,關(guān)于人類(lèi)高血壓全基因組的甲基化研究還鮮有報(bào)道。本論文的第一分題從全基因組水平在極端高血壓和完美對(duì)照組之間,高血壓前期未轉(zhuǎn)化和轉(zhuǎn)化組之間比較了外周血DNA甲基化譜的差異,并從兩者的交集中找到了兩個(gè)可能與高血壓發(fā)病機(jī)制相關(guān)的DNA甲基化差異位點(diǎn),并做了初步功能研究。同時(shí),選取與中國(guó)人群高血壓相關(guān)的GWAS陽(yáng)性位點(diǎn),初步探索了DNA甲基化修飾作用對(duì)表型的影響。 方法：選取來(lái)自于山東省日照社區(qū)的44例完美對(duì)照,44例極端高血壓患者,44例前期高血壓樣本,采用Illumina450K BeadChip甲基化芯片檢測(cè)所有個(gè)體的外周血DNA甲基化狀態(tài)。采用焦磷酸測(cè)序技術(shù)重復(fù)第一人群芯片結(jié)果,隨后在擴(kuò)大的70例完美對(duì)照和133例高血壓病例中驗(yàn)證陽(yáng)性的CpG甲基化位點(diǎn)。經(jīng)兩階段的篩選找出與高血壓相關(guān)的OVGP1基因。ELISA檢測(cè)高血壓與對(duì)照組間的血漿OVGP1蛋白水平。實(shí)時(shí)熒光定量PCR、Western-blot和免疫熒光實(shí)驗(yàn)用于檢測(cè)OVGP1在內(nèi)皮細(xì)胞的表達(dá)。進(jìn)一步用pull-down實(shí)驗(yàn)捕獲與OVGP1相互作用的蛋白,并用慢病毒轉(zhuǎn)染HUVEC和THP1細(xì)胞,高表達(dá)OVGP1,檢測(cè)高血壓相關(guān)分子的mRNA水平變化。另一方面,用SNPshot法對(duì)第一階段的高血壓和對(duì)照人群分析rs1842896和rs7136259兩個(gè)位點(diǎn)的基因型,結(jié)合DNA甲基化數(shù)據(jù),分析表觀遺傳、遺傳變異和表型的關(guān)系。 結(jié)果：在全基因組DNA甲基化篩選階段共有14個(gè)甲基化差異位點(diǎn)在完美對(duì)照和極端高血壓、高血壓前期未轉(zhuǎn)化和轉(zhuǎn)化兩個(gè)病例對(duì)照中均有顯著差異,并且甲基化升高或降低的趨勢(shì)相同。在焦磷酸測(cè)序驗(yàn)證后,分別位于OVGP1和CPO基因啟動(dòng)子區(qū)的cg20823859和cg17600943位點(diǎn)的甲基化水平在高血壓病例中均顯著降低,平均甲基化差異分別為-0.11和-0.10,校正年齡、性別和BMI后仍具有顯著性(P=0.02和P=0.001)。血漿中OVGP1蛋白水平在高血壓人群中也顯著高于對(duì)照組。OVGP1基因的功能初探結(jié)果顯示,OVGP1在HUVEC胞漿中表達(dá),通過(guò)pull-down捕獲到25個(gè)可能與OVGP1相互作用的蛋白,其中4個(gè)蛋白與高血壓的病理過(guò)程顯著相關(guān)。進(jìn)一步研究發(fā)現(xiàn)OVGP1表達(dá)升高可使HUVEC和THP1中TGF-β1和GF-β2的mRNA水平分別升高。 基因分型結(jié)果顯示,已知的中國(guó)高血壓人群易感位點(diǎn)rs1842896在88例高血壓病人和對(duì)照中的分布頻率具有顯著性差異(P0.05)。攜帶有TT基因型的個(gè)體中,極端高血壓患者在cg21176026位點(diǎn)的甲基化程度也顯著低于完美對(duì)照(P0.05),而TG+GG基因型的個(gè)體中兩組無(wú)差異(P=0.39)。進(jìn)一步我們發(fā)現(xiàn),以DNA甲基化程度β=0.75為臨界點(diǎn),TT基因型攜帶者并伴隨低甲基化狀態(tài)發(fā)生高血壓的幾率增高,提示cg21176026位點(diǎn)的甲基化修飾可影響高血壓危險(xiǎn)等位基因rs1842896-T的作用。 結(jié)論：本研究采用全基因組甲基化研究策略,初步證明表觀遺傳調(diào)控可能參與高血壓的發(fā)生發(fā)展,并找到兩個(gè)與高血壓發(fā)病相關(guān)的新靶基因OVGP1和CPO。本研究也探索了遺傳變異、表觀遺傳修飾和高血壓的關(guān)系,并推斷了可能的相互作用模型。但是深入的分子機(jī)制仍需進(jìn)一步研究。 目的：尿酸是嘌呤的代謝終產(chǎn)物。過(guò)多的攝取富含嘌呤和果糖的食物已成為目前尿酸水平升高,繼而出現(xiàn)高尿酸血癥的重要原因。高尿酸血癥除了引起痛風(fēng),還被認(rèn)為是高血壓、心臟病、腎病和腦卒中的重要危險(xiǎn)因素之一。尿酸水平的升高常常先于高血壓出現(xiàn),提示尿酸作為獨(dú)立的內(nèi)源性環(huán)境因素,直接參與了導(dǎo)致高血壓的病理生理過(guò)程。本研究采用全基因組DNA甲基化差異篩選策略,研究高尿酸導(dǎo)致高血壓的表觀遺傳機(jī)制。 方法：選取來(lái)自于山東省日照社區(qū)的12例高尿酸血癥患者,44例完美對(duì)照,44例極端高血壓患者,采用Illumina450K BeadChip甲基化芯片檢測(cè)所有外周血DNA甲基化狀態(tài)。首先從高尿酸血癥患者和完美對(duì)照外周血DNA中尋找與高尿酸血癥相關(guān)的DNA甲基化差異位點(diǎn),進(jìn)一步與極端高血壓和完美對(duì)照間的DNA甲基化差異位點(diǎn)取交集,獲得7個(gè)在兩組比較中DNA甲基化變化一致的位點(diǎn)。隨后,在體外用尿酸刺激細(xì)胞,檢測(cè)與差異甲基化位點(diǎn)臨近基因的mRNA表達(dá)水平的改變。 結(jié)果：獲得7個(gè)可能參與高尿酸導(dǎo)致高血壓發(fā)病機(jī)制相關(guān)的DNA甲基化差異位點(diǎn)。其中cg15711973、 cg23812489、 cg02157463和cg23947654位點(diǎn)在高尿酸血癥和極端高血壓患者中甲基化程度均降低,eg12252547、 cg06827234和cg16051083也在兩個(gè)病例組中均升高。體外實(shí)驗(yàn)顯示,尿酸的刺激可以使THP1和Jurkat兩種免疫細(xì)胞內(nèi)FLG2的mRNA表達(dá)水平顯著升高。這與甲基化芯片中,位于FLG2上游TSS1500區(qū)CpG位點(diǎn)cg23812489的甲基化水平降低的結(jié)果是相符的。位于MAL2啟動(dòng)子區(qū)的cg12252547位點(diǎn)在芯片結(jié)果中病例組的甲基化水平高于對(duì)照組,在體外尿酸刺激下,能使THP1細(xì)胞中MAL2的mRNA水平降低,但Jurkat細(xì)胞中MAL2的表達(dá)水平?jīng)]有顯著改變。cg02157463位點(diǎn)處于JPH3基因的基因體區(qū),在病人體內(nèi)甲基化程度升高,相對(duì)應(yīng)地,當(dāng)尿酸刺激THP1和Jurkat細(xì)胞時(shí),JPH3的mRNA水平顯著降低。但是,我們并沒(méi)有檢測(cè)到其它的候選基因(TANC1, PCDHA, ZDHHC14) mRNA表達(dá)水平的改變。 結(jié)論：本研究采用全基因組DNA甲基化差異位點(diǎn)篩選研究策略,獲得了6個(gè)可能與高尿酸導(dǎo)致高血壓發(fā)病相關(guān)聯(lián)的候選基因。這些基因多與鈣離子相關(guān)通路和神經(jīng)信號(hào)傳遞有關(guān),提示尿酸升高有可能通過(guò)改變基因組中這些基因的DNA甲基化程度,調(diào)節(jié)基因表達(dá)水平,繼而參與高尿酸導(dǎo)致高血壓的致病過(guò)程。 本論文的第一部分研究了高血壓發(fā)生發(fā)展過(guò)程中表觀遺傳學(xué)調(diào)控機(jī)制,在本部分將探討高血壓引起的最為主要的并發(fā)癥之一——腦卒中的遺傳危險(xiǎn)因素。由于高血壓可直接引起顱內(nèi)動(dòng)脈瘤或血管畸形的破裂而發(fā)生出血性腦卒,且顱內(nèi)動(dòng)脈瘤的病因中遺傳因素占據(jù)了更主導(dǎo)的地位,因此本部分將以顱內(nèi)動(dòng)脈瘤為模型,研究高血壓并發(fā)癥的遺傳危險(xiǎn)因素。 顱內(nèi)動(dòng)脈瘤的破裂能夠?qū)е聡?yán)重的致死性后果。多項(xiàng)全基因組關(guān)聯(lián)研究(genome-wide association studies, GWAS)已經(jīng)在歐洲人群完成,但是迄今還沒(méi)有在中國(guó)漢族人群開(kāi)展顱內(nèi)動(dòng)脈瘤GWAS研究的報(bào)道。為驗(yàn)證歐洲顱內(nèi)動(dòng)脈瘤GWAS關(guān)聯(lián)研究發(fā)現(xiàn)的新易感位點(diǎn),本研究在大樣本的中國(guó)漢人群中調(diào)查了10個(gè)單核苷酸多態(tài)性(single nucleotide polymorphism, SNP)位點(diǎn)與顱內(nèi)動(dòng)脈瘤的關(guān)聯(lián)性。 選取649例中國(guó)漢族散發(fā)顱內(nèi)動(dòng)脈瘤患者和1682名正常人,對(duì)GWAS研究中已報(bào)道的10個(gè)候選易感位點(diǎn)采用時(shí)間飛行質(zhì)譜生物芯片系統(tǒng)(Sequenom MassArray)進(jìn)行基因分型。采用X2檢驗(yàn)、logistic回歸分析對(duì)SNP位點(diǎn)的基因型、等位基因進(jìn)行相關(guān)性分析。結(jié)果顯示,攜帶rs12413409-G和rs1980781-C等位基因的個(gè)體在病例和對(duì)照組中的頻率具有顯著差異(均為P=0.002),并使患顱內(nèi)動(dòng)脈瘤的風(fēng)險(xiǎn)分別增加1.27和1.26倍,并達(dá)到Bonferroni校正的檢驗(yàn)水準(zhǔn)。在加性遺傳模式下,rs12413409和rs1980781也與顱內(nèi)動(dòng)脈瘤顯著相關(guān)(分別為OR=1.27,95%CI1.09-1.48, P=0.002和OR=1.26,95%CI1.09-1.45, P=0.002)。進(jìn)一步按照年齡、破裂與未破裂、動(dòng)脈瘤的數(shù)量分層后發(fā)現(xiàn),在小于60歲的個(gè)體中上述兩個(gè)易感位點(diǎn)與顱內(nèi)動(dòng)脈瘤的關(guān)聯(lián)性增強(qiáng)。在等位基因和加性遺傳模型的關(guān)聯(lián)分析中,rs12413409和rs1980781可使顱內(nèi)動(dòng)脈瘤的破裂風(fēng)險(xiǎn)分別增加1.25倍和1.24倍(P0.005)。攜帶rs12413409-G和rs1980781-C的個(gè)體也更傾向于罹患單發(fā)的顱內(nèi)動(dòng)脈瘤。而之前GWAS研究報(bào)道的其它8個(gè)易感基因在本研究中并未顯示與中國(guó)漢人群顱內(nèi)動(dòng)脈瘤具有關(guān)聯(lián)性。 本研究驗(yàn)證了歐洲人群GWAS研究獲得的rs12413409和rs1980781兩個(gè)易感位點(diǎn),提示它們可能是中國(guó)漢人群顱內(nèi)動(dòng)脈瘤的遺傳風(fēng)險(xiǎn)因素之一。
[Abstract]:Objective:Cardiovascular and cerebrovascular diseases are one of the most important threats to human health.Hypertension is the most important risk factor of cardiovascular and cerebrovascular diseases and has become a heavy social burden in China.Therefore,the occurrence,development and prognosis of hypertension are still the key to the prevention and treatment of hypertension.Studies have shown that hypertension is an interaction of genetic and environmental factors. Complex diseases. Candidate gene strategies and all susceptibility loci obtained from genome-wide association studies have not shown a strong association with hypertension. The etiology of hypertension remains uncertain. In recent years, epigenetic studies of hypertension have found clues that may be able to communicate environmental factors with the nuclear genome. DNA methylation is one of the four important ways of epigenetic regulation. However, in the field of hypertension, DNA methylation research has many problems to be solved urgently. The first part of this paper compares the differences of DNA methylation profiles in peripheral blood at the whole genome level between the extreme hypertension and the perfect control group, between the untransformed and untransformed pre-hypertension groups, and finds two possible sites of DNA methylation differences associated with the pathogenesis of hypertension from their intersection. At the same time, the effect of DNA methylation modification on phenotype was preliminarily explored by selecting GWAS positive sites associated with hypertension in Chinese population.
METHODS: Forty-four perfect controls, 44 patients with extreme hypertension and 44 patients with pre-hypertension were selected from Rizhao community in Shandong Province. DNA methylation status in peripheral blood of all individuals was detected by Illumina 450K Bead Chip methylation chip. Pyrophosphate sequencing technique was used to repeat the results of the first population chip, and then the enlarged 70 cases were perfect. Positive CpG methylation sites were identified in 133 hypertensive patients and controls. OVGP1 gene associated with hypertension was identified by two-stage screening. Plasma levels of OVGP1 protein were detected by ELISA. Real-time fluorescence quantitative PCR, Western-blot and immunofluorescence assays were used to detect the expression of OVGP1 in endothelial cells. The ull-down assay captured the protein interacting with OVGP1 and transfected HUVEC and THP1 cells with lentiviruses to overexpress OVGP1 and detect the changes of mRNA levels of hypertension-related molecules. The relationship between epigenetics, genetic variation and phenotype was analyzed.
Results: A total of 14 methylation sites were found in perfect control and hypertensive patients during the whole genome DNA methylation screening stage, and there were significant differences between the untransformed and untransformed pre-hypertension patients, and the trend of methylation increased or decreased was the same. The methylation levels at Cg20823859 and Cg17600943 loci were significantly lower in hypertensive patients, with mean methylation differences of - 0.11 and - 0.10, respectively. Age, sex and BMI were adjusted for significant differences (P = 0.02 and P = 0.001). The plasma level of OVGP1 protein was also significantly higher in hypertensive patients than in the control group. The results showed that OVGP1 was expressed in the cytoplasm of HUVEC, and 25 proteins possibly interacting with OVGP1 were captured by pull-down. Four of these proteins were significantly correlated with the pathological process of hypertension.
The results of genotyping showed that the distribution frequency of the known susceptibility locus rs1842896 in 88 hypertensive patients and controls was significantly different (P 0.05). In individuals with TT genotype, the methylation level of cg21176026 locus in patients with extreme hypertension was also significantly lower than that of the perfect control (P 0.05), and the TG + GG genotype was significantly lower than that of the control (P 0.05). There was no significant difference between the two groups (P = 0.39). Further, we found that when DNA methylation level beta = 0.75 was the critical point, TT genotype carriers were more likely to develop hypertension accompanied by hypomethylation, suggesting that methylation modification at cg21176026 site could affect the role of the risk allele rs1842896-T for hypertension.
CONCLUSION: The genome-wide methylation strategy was used to preliminarily demonstrate that epigenetic regulation may be involved in the development of hypertension, and two novel target genes, OVGP1 and CPO, were identified. The relationship between genetic variation, epigenetic modification and hypertension was explored, and possible interactions were inferred. However, further research is needed on the molecular mechanism.
Objective: Uric acid is the end product of purine metabolism. Excessive intake of food rich in purine and fructose has become an important cause of increased uric acid levels and subsequent hyperuricemia. Hyperuricemia is considered to be an important risk factor for hypertension, heart disease, kidney disease and stroke in addition to gout. High levels often precede hypertension, suggesting that uric acid, as an independent endogenous environmental factor, is directly involved in the pathophysiological process leading to hypertension.
Methods: 12 hyperuricemia patients, 44 perfect controls and 44 hypertensive patients were selected from Rizhao community of Shandong Province. DNA methylation status of all peripheral blood samples was detected by Illumina 450K Bead Chip methylation chip. DNA related to hyperuricemia was first searched from the DNA of hyperuricemia patients and perfect control peripheral blood samples. The methylation difference sites were further intersected with the DNA methylation difference sites between extreme hypertension and perfect control to obtain seven sites with the same changes in DNA methylation in both groups.
Results: Seven different DNA methylation sites were identified, including Cg15711973, Cg23812489, Cg02157463 and Cg23947654, which may be involved in the pathogenesis of hyperuricemia and hypertension. The levels of DNA methylation were decreased in both hyperuricemia and hypertensive patients, and increased in eg12252547, cg06827234 and cg16051083. In vitro experiments showed that uric acid stimulation significantly increased the expression of FLG2 mRNA in THP1 and Jurkat immune cells. This was consistent with the decrease of methylation level at CpG site cg23812489 in TSS1500 region upstream of FLG2 on the methylation chip. The cg12252547 site in the promoter region of MAL2 was found in the case group. The level of methylation was higher than that of the control group. Under uric acid stimulation in vitro, the level of MAL2 mRNA in THP1 cells decreased, but the level of MAL2 expression in Jurkat cells did not change significantly. However, we did not detect any changes in the expression levels of other candidate genes (TANC1, PCDHA, ZDHHC14).
CONCLUSION: Six candidate genes were identified by genome-wide DNA methylation differential site screening strategy. These genes are mostly related to calcium ion-related pathways and neural signal transduction, suggesting that elevated uric acid may alter the DNA methylation of these genes in the genome. Degree of regulation, gene expression level, and then participate in the pathogenesis of hypertension induced by hyperuricemia.
The first part of this paper studies the epigenetic regulation mechanism in the development of hypertension. In this part, we will explore the genetic risk factors of stroke, one of the most important complications of hypertension. Hereditary factors play a more dominant role in the etiology of intracranial aneurysms, so this part will study the genetic risk factors of hypertension complications with intracranial aneurysms as a model.
Several genome-wide association studies (GWAS) have been performed in European populations, but so far no GWAS studies have been carried out in Chinese Han population. To verify the new findings of the GWAS association study for intracranial aneurysms in Europe This study investigated the association of 10 single nucleotide polymorphism (SNP) loci with intracranial aneurysms in a large sample of Chinese Han population.
A total of 649 Chinese Han sporadic intracranial aneurysms and 1682 normal subjects were selected for genotyping of 10 candidate susceptibility sites reported in the GWAS study using Sequenom Mass Array. The results showed that the frequencies of rs12413409-G and rs1980781-C alleles were significantly different between the case group and the control group (both P = 0.002), and the risk of intracranial aneurysms was increased by 1.27 and 1.26 times respectively, reaching the Bonferroni-calibrated test level. There was a significant association (OR = 1.27, 95% CI 1.09-1.48, P = 0.002 and OR = 1.26, 95% CI 1.09-1.45, P = 0.002, respectively). Further stratification of ruptured and unruptured aneurysms by age and number of aneurysms revealed an increased association between these two susceptibility loci and intracranial aneurysms in individuals younger than 60 years of age. In the analysis, rs12413409 and rs1980781 increased the risk of rupture of intracranial aneurysms by 1.25 and 1.24 times respectively (P 0.005). Individuals carrying rs12413409-G and rs1980781-C were also more likely to develop single intracranial aneurysms. The other eight susceptibility genes reported in the previous GWAS study did not show intracranial motility in Chinese Han population. Aneurysms are associated.
This study confirmed two susceptibility loci, rs12413409 and rs1980781, obtained from the GWAS study in European populations, suggesting that they may be one of the genetic risk factors for intracranial aneurysms in Chinese Han population.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R743.2

【相似文獻(xiàn)】

中國(guó)期刊全文數(shù)據(jù)庫(kù) 前10條

1 李偉;;《表觀遺傳學(xué)》教學(xué)內(nèi)容設(shè)計(jì)[J];中外醫(yī)療;2008年35期

2 文玉;李曉燕;;DNA甲基化與結(jié)直腸癌[J];醫(yī)學(xué)綜述;2011年17期

3 夏鴻彬,程斌,洪筠,李春陽(yáng),楊靈瀾,葉萍;口腔癌前損害和鱗癌組織hMSH2轉(zhuǎn)錄水平改變與意義[J];中國(guó)腫瘤臨床與康復(fù);2003年04期

4 張永彪,褚嘉yP;表觀遺傳學(xué)與人類(lèi)疾病的研究進(jìn)展[J];遺傳;2005年03期

5 劉棣;蔡建春;;DNA異常甲基化在腫瘤中的作用[J];醫(yī)學(xué)綜述;2006年10期

6 王愛(ài)東;黃強(qiáng);;表觀遺傳學(xué)改變與膠質(zhì)瘤發(fā)生的分子關(guān)系[J];中華實(shí)驗(yàn)外科雜志;2006年12期

7 董暉;鐘麗;孫興旺;;腫瘤DNA甲基化的臨床應(yīng)用進(jìn)展[J];實(shí)用癌癥雜志;2007年05期

8 陳麗;屈衛(wèi)東;;DNA甲基化及其芯片技術(shù)研究進(jìn)展[J];國(guó)外醫(yī)學(xué)(衛(wèi)生學(xué)分冊(cè));2007年06期

9 陳美霞;孟元光;韓為東;趙亞力;;DNA甲基化在子宮內(nèi)膜癌中的研究進(jìn)展[J];國(guó)外醫(yī)學(xué)(婦產(chǎn)科學(xué)分冊(cè));2007年06期

10 杜麗;;Millipore 2008亞洲生物高峰論壇在京召開(kāi)[J];中國(guó)生物化學(xué)與分子生物學(xué)報(bào);2008年03期

中國(guó)重要會(huì)議論文全文數(shù)據(jù)庫(kù) 前10條

1 盛樹(shù)力;;表觀遺傳學(xué)看老年性癡呆發(fā)病機(jī)理、診斷和防治前景[A];2009全國(guó)抗衰老與老年癡呆學(xué)術(shù)會(huì)議論文匯編[C];2009年

2 陳敏;崔盤(pán)根;林麟;姚煦;;表觀遺傳學(xué)揭開(kāi)復(fù)雜皮膚病奧秘的新希望?[A];中華醫(yī)學(xué)會(huì)第十五次全國(guó)皮膚性病學(xué)術(shù)會(huì)議論文集[C];2009年

3 盛樹(shù)力;;AD、腦老化和表觀遺傳學(xué)[A];東北三省生物化學(xué)與分子生物學(xué)學(xué)會(huì)2008年學(xué)術(shù)交流會(huì)論文摘要[C];2008年

4 徐金華;朱小華;施偉民;;SLE表觀遺傳學(xué)發(fā)病機(jī)制國(guó)內(nèi)外研究進(jìn)展[A];中華醫(yī)學(xué)會(huì)第十五次全國(guó)皮膚性病學(xué)術(shù)會(huì)議論文集[C];2009年

5 李陽(yáng)生;;表觀遺傳學(xué)——遺傳學(xué)一個(gè)新的分支[A];湖北省遺傳學(xué)會(huì)、江西省遺傳學(xué)會(huì)2006年學(xué)術(shù)年會(huì)暨學(xué)術(shù)討論會(huì)論文摘要集[C];2006年

6 盛樹(shù)力;;AD、腦老化和表觀遺傳學(xué)[A];2008年全國(guó)抗衰老與老年癡呆學(xué)術(shù)會(huì)議論文集[C];2008年

7 徐金華;朱小華;施偉民;;SLE表觀遺傳學(xué)發(fā)病機(jī)制國(guó)內(nèi)外研究進(jìn)展[A];2009全國(guó)中西醫(yī)結(jié)合皮膚性病學(xué)術(shù)會(huì)議論文匯編[C];2009年

8 魏光輝;吳盛德;林濤;李旭良;何大維;袁心剛;劉星;張德迎;陳柏林;;鄰苯二甲酸二(2-乙基己基)酯致隱睪發(fā)生的表觀遺傳學(xué)機(jī)制研究[A];中華醫(yī)學(xué)會(huì)第八次全國(guó)小兒外科學(xué)術(shù)會(huì)論文集[C];2010年

9 王漢成;;表觀遺傳學(xué)是功能基因在分子遺傳中的表現(xiàn)[A];中國(guó)遺傳學(xué)會(huì)功能基因組學(xué)研討會(huì)論文集[C];2006年

10 吳超群;;表觀遺傳學(xué)和人類(lèi)疾病[A];遺傳學(xué)進(jìn)步與人口健康高峰論壇論文集[C];2007年

中國(guó)重要報(bào)紙全文數(shù)據(jù)庫(kù) 前10條

1 記者 譚大躍　通訊員 王靜思;華大基因啟動(dòng)全球最大表觀遺傳學(xué)研究項(xiàng)目[N];深圳特區(qū)報(bào);2010年

2 夏洪平;表觀遺傳學(xué)——調(diào)控微環(huán)境抑制癌癥[N];健康報(bào);2007年

3 記者 易運(yùn)文;世界最大表觀遺傳學(xué)研究項(xiàng)目啟動(dòng)[N];光明日?qǐng)?bào);2010年

4 潘文;表觀遺傳學(xué)研究推動(dòng)生命科學(xué)進(jìn)步[N];中國(guó)醫(yī)藥報(bào);2008年

5 張獻(xiàn)懷;治惡性腫瘤可用表觀遺傳學(xué)藥物[N];健康報(bào);2010年

6 張獻(xiàn)懷;解放軍總醫(yī)院第一附屬醫(yī)院 采用表觀遺傳學(xué)療法治惡性胸水效果明顯[N];中國(guó)醫(yī)藥報(bào);2010年

7 本報(bào)實(shí)習(xí)生 劉張?chǎng)g 編譯;九大新興技術(shù)引領(lǐng)2006年[N];科技日?qǐng)?bào);2006年

8 記者 韓曉玲邋通訊員 金安江 范敬群;為花器官發(fā)育找到神奇“開(kāi)關(guān)”[N];湖北日?qǐng)?bào);2008年

9 陳英云　喬蕤琳 記者 趙宇清 見(jiàn)習(xí)記者 常春暉;重大疾病發(fā)現(xiàn)和治療有新突破[N];黑龍江日?qǐng)?bào);2010年

10 馬勤;中美科學(xué)家找到白血病抑制基因[N];中國(guó)醫(yī)藥報(bào);2007年

中國(guó)博士學(xué)位論文全文數(shù)據(jù)庫(kù) 前10條

1 黃金鳳;乙型肝炎病毒X蛋白相關(guān)原發(fā)性肝癌發(fā)生中的表觀遺傳學(xué)機(jī)制研究[D];第二軍醫(yī)大學(xué);2012年

2 張廣華;子宮內(nèi)膜癌細(xì)胞孕激素受體基因表觀遺傳學(xué)調(diào)控的研究-DNA甲基化及表達(dá)沉默相關(guān)的染色質(zhì)成分變化[D];天津醫(yī)科大學(xué);2010年

3 謝橋生;乳腺癌細(xì)胞中miR-146a表達(dá)調(diào)控的表觀遺傳學(xué)機(jī)制[D];第四軍醫(yī)大學(xué);2011年

4 王治香;小檗堿、地西他濱去甲基化調(diào)控急性髓系白血病細(xì)胞的逆轉(zhuǎn)耐藥作用及其機(jī)制探討[D];南方醫(yī)科大學(xué);2014年

5 鄭勇;間充質(zhì)干細(xì)胞自發(fā)轉(zhuǎn)化的表觀遺傳學(xué)機(jī)制研究[D];武漢大學(xué);2012年

6 蘇小平;shRNA誘導(dǎo)14-3-3σ基因啟動(dòng)子甲基化與基因表達(dá)沉默的研究[D];第二軍醫(yī)大學(xué);2006年

7 徐寶艷;HBV感染后表型相關(guān)單卵孿生子基因組CpG島差異甲基化基因的篩查[D];第三軍醫(yī)大學(xué);2006年

8 黃磊;COX-2在大連地區(qū)胃癌中的低頻率表達(dá)、甲基化狀態(tài)及其腫瘤遺傳學(xué)意義分析[D];大連醫(yī)科大學(xué);2006年

9 張美善;高梁葉片和胚乳DNA甲基化水平和模式的遺傳與變異研究[D];東北師范大學(xué);2007年

10 楊柳;后基因組學(xué)研究：?jiǎn)岱纫蕾?lài)的蛋白質(zhì)組學(xué)分析DNA甲基化譜分析技術(shù)的建立與評(píng)價(jià)[D];浙江大學(xué);2008年

中國(guó)碩士學(xué)位論文全文數(shù)據(jù)庫(kù) 前10條

1 冀勝軍;大鼠全腦照射后早期表觀遺傳學(xué)變化特征的研究[D];蘇州大學(xué);2011年

2 齊興;油菜雜種優(yōu)勢(shì)形成過(guò)程中基因組DNA甲基化模式研究[D];中國(guó)農(nóng)業(yè)科學(xué)院;2006年

3 黃軼群;PHI對(duì)淋巴母細(xì)胞性白血病Molt-4細(xì)胞株組蛋白調(diào)控的實(shí)驗(yàn)研究[D];福建醫(yī)科大學(xué);2006年

4 劉棣;胃癌相關(guān)基因啟動(dòng)子甲基化狀態(tài)的研究[D];福建醫(yī)科大學(xué);2006年

5 袁苗;應(yīng)用表觀遺傳學(xué)方法檢測(cè)母體循環(huán)中游離胎兒DNA[D];山東大學(xué);2007年

6 方芳;從基因組序列預(yù)測(cè)CpG島甲基化的傾向性[D];清華大學(xué);2007年

7 楊娟;DNA甲基化轉(zhuǎn)移酶DNMT1，DNMT3a，DNMT3b在子宮內(nèi)膜異位癥中的表達(dá)及意義[D];中南大學(xué);2008年

8 錢(qián)波;肝細(xì)胞癌多基因啟動(dòng)子區(qū)域異常甲基化的實(shí)驗(yàn)研究[D];安徽醫(yī)科大學(xué);2005年

9 魯爽;丙烯酰胺干擾大鼠精子發(fā)生表觀遺傳修飾的初步研究[D];中國(guó)協(xié)和醫(yī)科大學(xué);2006年

10 魏源華;APC基因甲基化特異性PCR檢測(cè)方法的建立及其在肺癌診斷中的應(yīng)用[D];南京醫(yī)科大學(xué);2006年

，

本文編號(hào)：2186068