本文選題：胰腺癌　切入點：SWI/SNF　出處：《華中科技大學(xué)》2015年博士論文　論文類型：學(xué)位論文

【摘要】：胰腺癌目前仍是預(yù)后差,死亡率極高的消化道惡性腫瘤,5年生存率小于5%。2008年,世界范圍內(nèi)估計新發(fā)病例為27萬多例,估計死亡病例為26萬多例,居全球惡性腫瘤死因的第8位。近年來,全求胰腺癌的發(fā)病率已趨平穩(wěn),而我國則呈上升趨勢,從70年代相對少見到2005年居常見惡性腫瘤死因的第7位。胰腺癌高病死率的現(xiàn)狀一直沒得到改善的重要原因是由于病因尚未清楚。目前手術(shù)切除是唯一可能的治愈方法,由于缺乏有效的早期診斷方法,多數(shù)病例確診時已是晚期,喪失手術(shù)切除機(jī)會。惡性腫瘤是一種慢性復(fù)雜性疾病,是環(huán)境和遺傳因素長期共同作用的結(jié)果。胰腺癌的家族聚集性提示遺傳因素在胰腺癌的發(fā)生過程中扮演重要角色。因此,開展胰腺癌的遺傳易感性研究,尋找特異敏感的生物標(biāo)志物應(yīng)用于早期診斷,評估療效及預(yù)后,以及應(yīng)用發(fā)展新的治療靶,對于我國胰腺癌的綜合防治具有重要意義。 第一部分SWI/SNF復(fù)合物的遺傳變異與胰腺癌發(fā)生風(fēng)險關(guān)系 研究背景：基因的異常轉(zhuǎn)錄是癌癥發(fā)生的基礎(chǔ),染色質(zhì)高度緊密的折疊阻止了轉(zhuǎn)錄因子、輔因子與DNA的結(jié)合,所以凡涉及DNA的反應(yīng)都要克服染色質(zhì)的高度緊密性。ATP依賴的染色質(zhì)重構(gòu)復(fù)合物是利用水解ATP獲得的能量來動員核小體,改變?nèi)旧|(zhì)的結(jié)構(gòu),使得轉(zhuǎn)錄因子與DNA結(jié)合,從而調(diào)節(jié)靶基因的轉(zhuǎn)錄。其中交配型轉(zhuǎn)換/蔗糖不發(fā)酵復(fù)合物(mating type switch/sucrose non-fermenting, SWI/SNF)蛋白家族廣泛參與細(xì)胞的分化、增殖和DNA修復(fù),作為腫瘤抑制基因被研究得最為深入,大量的研究發(fā)現(xiàn)在包括胰腺癌在內(nèi)的很多人類癌癥中都發(fā)現(xiàn)SWI/SNF復(fù)合物亞基的突變或表達(dá)異常。 研究目的：分析SWI/SNF復(fù)合物遺傳變異與中國漢族人群胰腺癌發(fā)生的關(guān)系；評價SWI/SNF復(fù)合物關(guān)鍵基因的遺傳變異基因-基因,基因-環(huán)境交互作用在于在胰腺癌發(fā)生過程中的效應(yīng)。 研究方法：采用兩階段病例-對照研究系統(tǒng)地分析ATP依賴的染色質(zhì)重構(gòu)復(fù)合物SWI/SNF基因的遺傳變異與中國人群胰腺癌發(fā)生風(fēng)險關(guān)系。第一階段在武漢地區(qū)中應(yīng)用中通量基因分型平臺OpenArray對SWI/SNF復(fù)合物關(guān)鍵基因的標(biāo)簽SNP(tag SNP)與胰腺癌發(fā)生關(guān)系進(jìn)行關(guān)聯(lián)研究,篩選出關(guān)聯(lián)SNPs;第二階段在北京地區(qū)用Taqman基因分型技術(shù)驗證第一階段的關(guān)聯(lián)SNPs。應(yīng)用卡方檢驗比較基因型及人口學(xué)資料分布；利用Armtage's趨勢檢驗進(jìn)行基因型與胰腺癌發(fā)生風(fēng)險的關(guān)聯(lián)分析：應(yīng)用logistic回歸進(jìn)行單位點分析計算各SNP的效應(yīng)值;為控制因多重檢驗而引入的假陽性率,采用錯誤發(fā)現(xiàn)率(False discovery rate,FDR)方法進(jìn)行多重假設(shè)檢驗校正；應(yīng)用lOgistic回歸對基因-基因和基因-環(huán)境交互作用進(jìn)行分析。 研究結(jié)果：1.第一階段納入310例胰腺癌病例與457位健康對照,共分析了編碼SWI/SNF復(fù)合物的6個關(guān)鍵基因上的14個SNP,以隱性遺傳模型計算,我們發(fā)現(xiàn)位于BRD7基因上的rs11644043(OR=2.04,95%CI=1.17-3.56)、 SMARCA4基因上的rs11085754(OR=1.64,95%CI=1.16-2.33)以及SMARCBl基因上的rs2073389(OR=1.93,95%CI=1.36-2.74)三個位點與胰腺癌發(fā)生風(fēng)險顯著相關(guān)：第二階段納入了429例胰腺癌病例與585位健康對照,成功驗證了rs11644043(OR=1.97,95%CI=1.24-3.14)和rs11085754(OR=1.45,95%CI=1.04-2.02)兩個位點。 2.兩階段合并,我們發(fā)現(xiàn)了三個位點rs11644043. rs11085754與rs2073389之間的對胰腺癌發(fā)生風(fēng)險作用的累積效應(yīng)(P for trend0.0001),個體隨著攜帶風(fēng)險基因型個數(shù)的增加,胰腺癌的發(fā)生風(fēng)險也隨之增加。 1.兩階段合并,我們發(fā)現(xiàn)rs2073389(Padd-FDR=6.00×10-4,Pmul-FDR=1.50×10-2)以及rs11085754(Padd-FDR=0.03)在修飾胰腺癌發(fā)生風(fēng)險方面都與吸煙存在著交互作用。 研究結(jié)論：1.位于BRD7基因上的rs11644043以及SMARCA4上rs11085754的遺傳變異和中國人群的胰腺癌發(fā)生風(fēng)險相關(guān)； 2. rs11644043、 rs11085754與位于SMARCB1基因上的rs2073389三者在對胰腺癌發(fā)生風(fēng)險方面存在著累積效應(yīng)； 3.rs2073389以及rs11085754在修飾胰腺癌發(fā)生風(fēng)險方面都與吸煙存在著交互作用。 創(chuàng)新點與不足之處：本研究采用兩階段病例對照研究設(shè)計首次在中國人群中探討SWI/SNF復(fù)合復(fù)上的遺傳變異和胰腺癌發(fā)生關(guān)系。重點分析了基因-基因、基因-環(huán)境交互作用,是以往很多研究所忽略的。 本研究的樣本量較小,特別是在研究基因-基因,基因-環(huán)境交互作用時,統(tǒng)計效能不足稍顯不足。本次研究中對發(fā)現(xiàn)的遺傳變異沒有進(jìn)行生物學(xué)功能實驗,所以其背后的生物學(xué)機(jī)制需要進(jìn)一步研究和驗證。第二部分9p21.3區(qū)域的遺傳變異與胰I腺癌發(fā)生風(fēng)險關(guān)系 研究背景：近來,9p21.3區(qū)域成為多種疾病的GWAS的熱點區(qū)域,如慢性淋巴細(xì)胞白血病、黑色素瘤、膠質(zhì)瘤、乳腺癌、心血管疾病、顱內(nèi)動脈瘤、子宮內(nèi)膜異位等。這一區(qū)段在30-40%的人類腫瘤中都發(fā)現(xiàn)失活,包含了人類三個重要的抑癌基因p16INK4a、 p14ARF、 P15INK4b,它們在調(diào)節(jié)細(xì)胞周期抑制、衰老、凋亡方面作用突出,廣泛參與到各種腫瘤的發(fā)生發(fā)展過程中。此區(qū)域的多個抑癌基因在胰腺癌的發(fā)生發(fā)展過程中扮演重要角色,目前,尚無研究報道探索這一區(qū)域的遺傳變異與中國人群胰腺癌發(fā)生風(fēng)險的關(guān)系。 研究目的：系統(tǒng)地分析9p21.3上的遺傳變異與中國漢族人群胰腺癌發(fā)生風(fēng)險的關(guān)系；對潛在的功能性位點進(jìn)行深入的功能學(xué)實驗研究,進(jìn)一步明確真正的致病位點的作用。 研究方法：首先,采用兩階段病例-對照研究研究設(shè)計,分析9p2113區(qū)域的遺傳變異與中國漢族人群胰腺癌發(fā)生風(fēng)險的關(guān)系,第一階段選取我們已完成的中國人群胰腺癌外顯子芯片中9p21.3(19.9-29Mb)區(qū)域的標(biāo)簽SNP,應(yīng)用卡方檢驗以及l(fā)ogistic回歸分析它們與胰腺癌發(fā)生風(fēng)險關(guān)系；得出與胰腺癌發(fā)生風(fēng)險相關(guān)的陽性的位點后,通過VISTA Enhancer Browser數(shù)據(jù)庫、Encode中chip-seq數(shù)據(jù)以及e-QTL數(shù)據(jù)庫SNPexp-A等生物信息分析手段分析此位點或與之連鎖的位點可能的潛在的功能：利用雙熒光素酶報告基因?qū)嶒炓约半娪具w移率變動分析實驗研究驗證這些位點的生物學(xué)功能；再對生物學(xué)功能實驗得出的潛在功能位點進(jìn)行第二階段的人群的關(guān)聯(lián)研究的驗證； 研究結(jié)果：1.第一階段我們納入了942例胰腺癌病例與1504例健康對照,分析了9p21.3區(qū)域的39個SNP,發(fā)現(xiàn)位于ANRIL基因上的rs6475609位點與胰腺癌發(fā)生風(fēng)險顯著相關(guān),每增加一個rs6475609-A等位基因,胰腺癌的發(fā)生風(fēng)險下降19%(OR=0.81,95%CI=0.72-0.92)。經(jīng)過生物信息學(xué)分析與關(guān)聯(lián)研究分析,發(fā)現(xiàn)與之高度連鎖的兩個可能存在潛在功能的位點rsl537373(OR=0.84,95%CI=0.74-0.95)與rs1333042(OR=0.84,95%CI=0.74-0.95)也與胰腺癌發(fā)生風(fēng)險顯著相關(guān)。第二階段我們對生物學(xué)功能實驗驗證出來的位點rsl537373進(jìn)行人群的關(guān)聯(lián)研究,納入了來自武漢地區(qū)的624例胰腺癌病例與1244例健康對照,發(fā)現(xiàn)rs1537373位點的遺傳變異仍和胰腺癌發(fā)生風(fēng)險顯著相關(guān),個體每增加一個rs1537373-T,發(fā)生胰腺癌的風(fēng)險下降16%(OR=0.84,95%CI=0.73-0.98)。 2.e-QTL分的結(jié)果顯示,rsl537373位點的遺傳變異與CDKN2B基因的表達(dá)水平相關(guān),攜帶TG/TT基因型的個體的CDKN2B的表達(dá)水平要顯著高于攜帶GG基因型的個體(P dominant:6.00×10-4)。 3.雙熒光素酶報告基因結(jié)果顯示,在胰腺癌的兩個細(xì)胞系Panc-1和SW1990中,都發(fā)現(xiàn)了含有rsl537373-G的片段較含有rsl537373-T的片段有更強(qiáng)的增強(qiáng)子活性(Ppanc-10.01,Psw19900.01)。 4.電泳遷移率變動實驗發(fā)現(xiàn),含有rs1537373-G的片段與某轉(zhuǎn)錄因子的結(jié)合能力強(qiáng)于含有rs1537373-T的片段。 研究結(jié)論：1.位于ANRIL基因上的rsl537373位點的遺傳變異與中國人群的胰腺癌發(fā)生風(fēng)險顯著相關(guān)； 2.rs1537373位點上的遺傳變異可能由于與某轉(zhuǎn)錄因子的結(jié)合活性不同,從而影響所在片段的增強(qiáng)子活性,進(jìn)而影響胰腺癌發(fā)生風(fēng)險。 創(chuàng)新點與不足之處：本研究采用兩階段的病例對照研究結(jié)合生物學(xué)功能實驗的策略首次系統(tǒng)全面地分析了9p21.3區(qū)域的功能性遺傳變異與中國人群胰腺癌發(fā)生風(fēng)險的關(guān)系。 本研究未能獲得胰腺癌病人的組織樣本,不能明確發(fā)現(xiàn)的陽性位點具體影響臨近的哪個基因的表達(dá),只能根據(jù)現(xiàn)的的數(shù)據(jù)庫的數(shù)據(jù)推測,證據(jù)級別稍顯不足。本次研究第二階段的樣本量較小,統(tǒng)計學(xué)效能稍顯不足。
[Abstract]:Pancreatic cancer is still poor prognosis and high mortality rate of malignant tumor of digestive tract, 5 years survival rate of less than 5%.2008, the worldwide estimated new cases of more than 270 thousand cases, estimates of deaths of more than 260 thousand cases of malignant tumor death worldwide eighth. In recent years, the global incidence of pancreatic cancer has become stable, while China is a rising trend, from 70s in 2005 to see relatively few common malignant tumor and the seventh leading cause of death. An important reason of high mortality rate of pancreatic cancer has not been improved because the cause is not yet clear. At present, surgical resection is the only cure for may, due to the lack of effective early diagnosis methods, the majority of cases the diagnosis is already late, lost the opportunity of surgery. Malignant tumor is a kind of chronic and complex disease, is the interaction of environmental and genetic factors. The pancreatic cancer familial aggregation suggest that genetic factors In play an important role in the process of pancreatic cancer. Therefore, to carry out genetic susceptibility to pancreatic cancer, looking for specific and sensitive biomarkers used for early diagnosis, curative effect evaluation and prognosis, and the target for the development of new applications, has important significance for the comprehensive prevention and treatment of pancreatic cancer in China.
The relationship between the genetic variation of SWI/SNF complex and the risk of pancreatic cancer
Background: abnormal transcription of genes is the basis of cancer, the highly condensed chromatin prevents the transcription factor binding cofactor and DNA, so the reaction involving DNA to overcome chromatin close.ATP dependent chromatin remodeling complex is the use of ATP hydrolysis energy mobilization nucleosome, alter the structure of chromatin, the transcription factor and DNA binding, thereby regulating the transcription of target genes. The mating type switching / sucrose non fermenting compound (mating type switch/sucrose non-fermenting SWI/SNF) protein family are widely involved in cell differentiation, proliferation and repair of DNA, as a tumor suppressor gene is the best studied. A large number of studies have found that SWI/SNF complex subunit found in many human cancers including pancreatic cancer, have the mutation or abnormal expression.
Objective: to analyze the relationship between the genetic variation of SWI/SNF complex and the occurrence of pancreatic cancer in Chinese Han population, and to evaluate the genetic variation of SWI/SNF complex gene gene gene interaction in the process of pancreatic cancer.
Methods: a case-control study of two stages of systematic analysis of genetic variation of chromatin remodeling complex SWI/SNF gene dependent ATP and pancreatic cancer risk Chinese population relationship. The first stage flux application in Wuhan area in genotyping platform OpenArray of SWI/SNF complex key gene tag SNP (tag SNP). With pancreatic cancer association studies, screening Association SNPs; the second stage is divided into the first stage of technology validation with Taqman gene in the Beijing area of the association of SNPs. chi square test was used to compare genotype distribution and demographic data; using the Armtage's trend test for correlation analysis of genotype and risk of pancreatic cancer: application of logistic regression unit analysis of the effects of calculated SNP value; false positive rate control for multiple testing are introduced, the false discovery rate (False discovery rate, FDR The method was corrected by multiple hypothesis test, and the interaction between gene gene and gene environment was analyzed by lOgistic regression.
Results: 1. the first stage included 310 cases of pancreatic cancer and 457 healthy controls, a total of 14 SNP were analyzed 6 key genes encoding SWI/SNF complexes on the in recessive genetic model, we found that the BRD7 gene located on the rs11644043 (OR=2.04,95%CI=1.17-3.56), SMARCA4 gene rs11085754 (OR=1.64,95%CI=1.16-2.33) and rs2073389 the SMARCBl gene (OR=1.93,95%CI=1.36-2.74) of the three loci with pancreatic cancer were significantly related to risk: the second stage included 429 cases of pancreatic cancer and 585 healthy controls, the successful validation of the rs11644043 (OR=1.97,95%CI=1.24-3.14) and rs11085754 (OR=1.45,95%CI=1.04-2.02) two loci.
2., in the two stage of consolidation, we found the cumulative effect of three loci rs11644043. rs11085754 and rs2073389 on the risk of pancreatic cancer (P for trend0.0001), and the risk of pancreatic cancer increased with the increase of risk genotype.
1., in the two stage of merger, we found that rs2073389 (Padd-FDR=6.00 * 10-4, Pmul-FDR=1.50 * 10-2) and rs11085754 (Padd-FDR=0.03) interact with cigarette smoking in modifying the risk of pancreatic cancer.
Conclusions: 1. the genetic variation of rs11644043 on the BRD7 gene and the genetic variation of rs11085754 on SMARCA4 is associated with the risk of pancreatic cancer in Chinese people.
2. rs11644043, rs11085754 and rs2073389 three on the SMARCB1 gene have cumulative effects on the risk of pancreatic cancer.
3.rs2073389 and rs11085754 interact with smoking in modifying the risk of pancreatic cancer.
Innovation and deficiency: This study used two stage case-control study design to investigate the relationship between SWI/SNF compound on genetic variation and pancreatic cancer in China population for the first time. The key point is the analysis of gene gene and gene environment interaction, is ignored by many previous studies.
In this study, the sample size is small, especially in the study of gene gene and gene environment interaction, lack of statistical power slightly insufficient. The study of genetic variation found no biological function experiment, so the biological mechanisms behind the need for further research and verification. The risk of relationship between genetic variation and pancreatic second part of the 9p21.3 region of I adenocarcinoma
Background: Recently, 9p21.3 has become a hot area of a variety of diseases such as GWAS, chronic lymphocytic leukemia, melanoma, glioma, breast cancer, cardiovascular disease, intracranial aneurysm, endometriosis. This segment is inactivated in 30-40% of human tumors, including three important human the tumor suppressor gene p16INK4a, p14ARF, P15INK4b, their aging in the regulation of cell cycle inhibition, apoptosis plays a prominent role, widely involved in the occurrence and development of tumors. Multiple tumor suppressor genes in this region in the development of pancreatic cancer plays an important role, at present, there is no report on the exploration of the relationship between risk the genetic variation in this region and Chinese pancreatic cancer population.
The purpose of this study is to systematically analyze the relationship between genetic variation on 9p21.3 and the risk of pancreatic cancer in Chinese Han population, and conduct in-depth functional experiments on potential functional sites, to further clarify the role of real pathogenic sites.
Research methods: firstly, the two stages of a case-control study design, analysis of the relationship between the risk of genetic variation in 9p2113 region and pancreatic cancer China Han population, the first stage of selection of pancreatic cancer China population we have completed the explicit 9p21.3 chip (19.9-29Mb) region of the SNP tag, using chi square test and logistic regression analysis of their relationship with the risk of pancreatic cancer; the risk associated with pancreatic cancer positive sites, through the VISTA Enhancer Browser database, Encode ChIP-seq database and e-QTL SNPexp-A and other biological information analysis method to analyze the site and the chain site may potentially function: using dual luciferase assay and electrophoresis mobility shift analysis Experimental study verified the biological function of these sites; and the biological function of the experiment The potential functional loci are verified by the association study of the second stage population.
Results: 1. the first phase we included 942 cases of pancreatic cancer and 1504 healthy controls, analyzed 39 SNP 9p21.3 region, found at risk was significantly related to ANRIL gene rs6475609 locus and pancreatic cancer, every increase of one rs6475609-A allele and the risk of pancreatic cancer decreased 19% (OR=0.81,95%CI=0.72-0.92) after analysis and association analysis of bioinformatics, found with highly linked two potentially functional sites of rsl537373 (OR=0.84,95%CI=0.74-0.95) and rs1333042 (OR=0.84,95%CI=0.74-0.95) also occurred and the risk of pancreatic cancer was significantly correlated. Second stage of our association study sites of rsl537373 biological function experimental verification of the crowd, included in the Wuhan area of 624 cases of pancreatic cancer and 1244 healthy controls, found that the genetic variation of rs1537373 locus and pancreas The risk of cancer was significantly correlated, and the risk of pancreatic cancer decreased by 16% (OR=0.84,95%CI=0.73-0.98) per individual increase of one rs1537373-T.
The results of 2.e-QTL analysis showed that the genetic variation of rsl537373 locus was related to the expression level of CDKN2B gene. The expression level of CDKN2B in individuals carrying TG/TT genotype was significantly higher than that in individuals carrying GG genotype (P dominant:6.00 * 10-4).
3. double luciferase reporter gene results showed that rsl537373-G and Panc-1 fragments were found in two cell lines of pancreatic cancer, including rsl537373-G and SW1990, which had stronger enhancer activity than those containing rsl537373-T (Ppanc-10.01, Psw19900.01).
4. electrophoretic mobility change experiments showed that the binding ability of rs1537373-G containing fragments to a transcription factor was better than that of rs1537373-T containing fragments.
Conclusions: 1. the genetic variation of the rsl537373 locus on the ANRIL gene is significantly associated with the risk of pancreatic cancer in the Chinese population.
Genetic variation on the 2.rs1537373 locus may be due to the different binding activity with a transcription factor, which affects the activity of the enhancer in the fragment and further affects the risk of pancreatic cancer.
Innovations and shortcomings: in this study, the two stage case-control study combined with the strategy of biological function experiment was used for the first time to systematically analyze the relationship between functional genetic variation in 9p21.3 region and the risk of pancreatic cancer in Chinese population.
This study failed to obtain tissue samples from patients with pancreatic cancer, the expression of which genes near the positive loci found the specific effect is not clear, only according to the database of data speculation, slightly less than the level of evidence. The second phase of the study sample size, statistical performance slightly less.

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R735.9

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 William CS CHO;南娟;;癌癥相關(guān)遺傳變異的新進(jìn)展及其在診斷研發(fā)中的意義[J];中國肺癌雜志;2011年01期

2 ;科學(xué)家發(fā)現(xiàn)遺傳變異可促進(jìn)高原適應(yīng)性[J];中國科技產(chǎn)業(yè);2012年07期

3 何毅勛,李新武;中國大陸日本血吸蟲品系的研究 Ⅶ.五地隔離群的遺傳變異及分化[J];中國寄生蟲學(xué)與寄生蟲病雜志;1992年01期

4 ;小鼠對雌激素破壞內(nèi)分泌作用的敏感性的遺傳變異[J];上海實驗動物科學(xué);1999年04期

5 ;不同地理區(qū)域的卡氏肺囊蟲(Pneumocystiscarinii)分離株遺傳變異與傳播的關(guān)系[J];中國人獸共患病雜志;2000年05期

6 劉莉娜;崔晶;姜鵬;王蕾;李靈招;張璽;王中全;;我國旋毛蟲地理株遺傳變異與系統(tǒng)發(fā)生關(guān)系的研究[J];中國人獸共患病學(xué)報;2011年11期

7 顧翔;;野生型HAV遺傳變異的流行病學(xué)模式[J];國外醫(yī)學(xué).流行病學(xué)傳染病學(xué)分冊;1992年02期

8 鄭世珍;李福祥;錢桂生;戢福云;;線粒體DNA遺傳變異與人類環(huán)境適應(yīng)性[J];中華肺部疾病雜志(電子版);2011年06期

9 張嬋娟;;千人基因組遺傳變異的整合圖譜[J];中國病理生理雜志;2013年11期

10 劉澤軍,魏明競,唐宏;乳本脫氫酶遺傳變異的篩選方法[J];中國現(xiàn)代醫(yī)學(xué)雜志;2000年12期

相關(guān)會議論文 前10條

1 劉莉娜;崔晶;姜鵬;王蕾;李靈招;張璽;王中全;;我國旋毛蟲地理株遺傳變異與系統(tǒng)發(fā)生關(guān)系的研究[A];中國畜牧獸醫(yī)學(xué)會家畜寄生蟲學(xué)分會第六次代表大會暨第十一次學(xué)術(shù)研討會論文集[C];2011年

2 張立玲;王全喜;馬勇華;劉佳森;;家畜抗病性遺傳變異的研究策略[A];全國養(yǎng)羊生產(chǎn)與學(xué)術(shù)研討會議論文集（2003～2004）[C];2004年

3 劉建波;劉長明;;豬輸血傳播病毒流行病學(xué)與遺傳變異的研究進(jìn)展[A];中國畜牧獸醫(yī)學(xué)會動物傳染病學(xué)分會第十二次人獸共患病學(xué)術(shù)研討會暨第六屆第十四次教學(xué)專業(yè)委員會論文集[C];2012年

4 李積友;劉霞;;甘肅灘羊地方種群遺傳變異及遺傳分化的生化遺傳學(xué)研究[A];中國遺傳學(xué)會七屆一次青年研討會暨上海高校模式生物E——研究院第一屆模式生物學(xué)術(shù)研討會論文匯編[C];2005年

5 盧一平;劉志洪;;2012ATC基礎(chǔ)研究熱點薈萃[A];2012中國器官移植大會論文匯編[C];2012年

6 張朋飛;侯玲靈;陳文;魯衛(wèi)衛(wèi);張淑平;康相濤;黃艷群;;雞線粒體ND1基因遺傳變異及其效應(yīng)的研究[A];中國畜牧獸醫(yī)學(xué)會家禽學(xué)分會第九次代表會議暨第十六次全國家禽學(xué)術(shù)討論會論文集[C];2013年

7 戴國俊;王金玉;王志躍;;新?lián)P州雞與萊航雞遺傳變異的RAPD分析[A];第四屆中國畜牧獸醫(yī)青年科技工作者學(xué)術(shù)研討會論文集[C];2001年

8 冀德君;;海拔壓力與中國牛屬MSTN基因的遺傳變異[A];中國畜牧獸醫(yī)學(xué)會家畜生態(tài)學(xué)分會第七屆全國代表大會暨學(xué)術(shù)研討會論文集[C];2008年

9 何慧婉;;探索空間環(huán)境對農(nóng)作物的影響 讓天上美食走進(jìn)我們的生活[A];中國空間科學(xué)學(xué)會空間探測專業(yè)委員會第十二次學(xué)術(shù)會議論文集[C];1999年

10 楊舒婷;李靜慧;陳露茜;趙云鵬;陳斌龍;傅承新;;遺傳變異對玄參的生長及化學(xué)多樣性的影響:基于同質(zhì)園實驗[A];第十屆全國藥用植物及植物藥學(xué)術(shù)研討會論文摘要集[C];2011年

相關(guān)重要報紙文章 前10條

1 記者 劉霞;遺傳飲食傾向影響肥胖[N];科技日報;2008年

2 記者 吳晉娜 通訊員 熊學(xué)莉 吳劉佳;我科學(xué)家發(fā)現(xiàn)遺傳變異可促進(jìn)高原適應(yīng)性[N];科技日報;2012年

3 記者 關(guān)媛媛　李志峰;世界首張家蠶高精度遺傳變異圖譜繪就[N];重慶日報;2009年

4 記者毛磊;百歲壽星遺傳變[N];人民日報;2003年

5 記者 毛磊;長命百歲原因之一[N];新華每日電訊;2003年

6 陳丹　劉霞;與生物衰老有關(guān)的遺傳變異首次獲得確認(rèn)[N];科技日報;2010年

7 林東昕;為什么有的人容易得癌癥？[N];科技日報;2009年

8 毛磊;科學(xué)界聯(lián)手出擊國際遺傳變異圖譜計劃[N];中國高新技術(shù)產(chǎn)業(yè)導(dǎo)報;2002年

9 記者 黃強(qiáng) 通訊員 熊學(xué)莉 吳劉佳;遺傳變異可促進(jìn)高原適應(yīng)性[N];工人日報;2012年

10 記者　張建松;我科學(xué)家繪制中國人21號染色體遺傳變異圖譜[N];新華每日電訊;2006年

相關(guān)博士學(xué)位論文 前9條

1 黃桂華;柚木種質(zhì)資源遺傳變異和優(yōu)良無性系早期選擇的研究[D];中國林業(yè)科學(xué)研究院;2015年

2 朱貝貝;中國人群胰腺癌遺傳易感性研究[D];華中科技大學(xué);2015年

3 李東;蠶類基因組與線粒體組高精度遺傳變異圖譜的構(gòu)建及其研究[D];西南大學(xué);2011年

4 王t，

本文編號：1628021