本文選題：全基因組關(guān)聯(lián)分析(GWAS) + 高鎂相關(guān)位點�。� 參考：《中國農(nóng)業(yè)科學(xué)院》2017年博士后論文

【摘要】：深度的全基因組關(guān)聯(lián)分析方法Open GWAS algorithm(OATH)為響應(yīng)遺傳學(xué)界的開源趨勢,我們開發(fā)了一種新的線性回歸方法用于全基因組關(guān)聯(lián)分析研究(GWAS),我們將其命名為開放GWAS算法(OATH)。該算法可以在不需要個體水平數(shù)據(jù)的情況下,僅使用自然匯總統(tǒng)計(NSS),不僅能完整的重現(xiàn)單一實驗?zāi)Ｐ偷膱蟾娼Y(jié)果,還能生成被掩藏或者未報道的其他模型下的結(jié)果。使用NSS,我們可以1、重復(fù)出于使用個體水平數(shù)據(jù)同樣精確度的GWAS結(jié)果,2、恢復(fù)出未報道的使用任何組合協(xié)變量的結(jié)果,3、深度評估結(jié)果,比如分析p值得方差,進(jìn)而得出一個更加可靠的評估結(jié)果,如同我們使用3種供鎂條件下的42個擬南芥表型數(shù)據(jù)所展示的結(jié)果。此外,OATH方法可以用于多中心聯(lián)合的GWAS meta研究,可以極大的提高GWAMA研究的靈活性。OATH的原型已在軟件 GEnetic Analysis Repository(GEAR,https://github.com/gc5k/GEAR)中實現(xiàn)。擬南芥不同生態(tài)型對高鎂的響應(yīng)某些蛇紋石土壤或半干旱地區(qū)土壤中的高鎂是作物生長發(fā)育的重要障礙。然而高鎂穩(wěn)態(tài)下植物適應(yīng)的具體遺傳位點和機(jī)理尚未很好的了解。利用388份收集自世界各地的擬南芥生態(tài)型材料和約25萬個SNP的基因型數(shù)據(jù),我們成功的找到了 109和74個分別在正常鎂(1OOOuM)和高鎂(1OOOOuM)與營養(yǎng)性狀相關(guān)的基因位點。超過90%的SNP與營養(yǎng)表型有關(guān),僅有2個SNP同時在正常鎂和高鎂條件下被定位到。在高鎂下發(fā)現(xiàn)一個與植株Ca濃度表型強(qiáng)相關(guān)的SNP位于候選基因Atlg60420(6tNRX1)中。進(jìn)一步的研究顯示,相較于野生型,Atnrx1突變體在高鎂供應(yīng)下具有較高的胞內(nèi)鈣濃度,較長的主根和積累更多的鮮重。這表明AtNRX1基因特異性的負(fù)向調(diào)節(jié)Ca的吸收和植株生長。此外,GWAS找到的其它SNP位點將有助于確定早期營養(yǎng)相關(guān)的生物標(biāo)志基因和分組育種標(biāo)記從而幫助開發(fā)鎂營養(yǎng)高效作物。水稻鎂相關(guān)同源基因挖掘針對擬南芥中定位的鎂相關(guān)的基因位點,我們利用水稻基因組信息,比對后鑒定了一些水稻同源基因。通過GWAS定位,我們一共613個顯著SNP位點區(qū)段,并預(yù)測篩選了 431個候選基因。通過同源比對,尋找在水稻中的直系同源基因,最終一共找到424個水稻同源基因。已克隆基因表明通過GWAS定位發(fā)現(xiàn)的表型關(guān)聯(lián)基因至少部分可以通過同源比對分析在水稻中找到相似功能的基因。此外,進(jìn)一步分析了剩余未克隆的水稻基因的表達(dá)以及其與表型的關(guān)系,發(fā)現(xiàn)種子萌發(fā)和鮮重以及上胚軸長度的基因以及鈉和鈣含量的基因存在較為可能的同源基因。
[Abstract]:Open GWAS algorithm (OATH), in response to the open source trend of the genetic community, has developed a new linear regression method for whole genome association analysis (GWAS). We named it as an open GWAS algorithm (OATH). This algorithm can only be made without the need for individual level data. Natural summary statistics (NSS) can not only reproduce the results of the single experimental model completely, but also generate the results under other models that are hidden or unreported. Using NSS, we can 1, repeat out of the GWAS results using the same accuracy of the individual level data, 2, and restore the unreported results of using any combinatorial covariance, 3 The results of the depth assessment, such as the analysis of the P worth of variance, and then a more reliable evaluation result, like the results shown in the 42 Arabidopsis phenotypic data of 3 kinds of magnesium supply conditions. In addition, the OATH method can be used in the multi center joint GWAS meta study, which can greatly improve the prototype of the flexibility.OATH of GWAMA research. It has been implemented in the software GEnetic Analysis Repository (GEAR, https://github.com/gc5k/GEAR). The high magnesium response to high magnesium in different ecotypes of Arabidopsis thaliana is an important obstacle to the growth and development of crops. However, the specific genetic sites and mechanisms of plant adaptation in high magnesium steady state are not very good. With 388 copies of Arabidopsis ecotype materials and about 250 thousand SNP genotype data collected from all over the world, we have successfully found 109 and 74 gene loci related to normal magnesium (1OOOuM) and high magnesium (1OOOOuM). More than 90% of SNP is associated with nutritional phenotypes, and only 2 SNP at the same time in normal magnesium and high magnesium Under high magnesium, a strong correlation between Ca concentration and SNP was found in the candidate gene Atlg60420 (6tNRX1). Further studies showed that, compared to the wild type, the Atnrx1 mutant had higher intracellular calcium concentration, longer main root and more fresh weight under the high magnesium supply. This indicated that the AtNRX1 gene was specific. Sexual negative regulation of Ca absorption and plant growth. In addition, the other SNP sites found by GWAS will help to identify early nutrition related biomarker genes and group breeding markers to help develop magnesium nutritive crops. Rice genome information was identified and some rice homologous genes were identified. Through GWAS location, we had 613 significant SNP loci segments and predicted and screened 431 candidate genes. Through homologous alignment, we searched for the direct homologous genes in rice, and finally found 424 rice homologous genes. The cloned genes showed that the gene was located by GWAS. The present phenotypic associated genes may at least partially find similar genes in Rice by homologous comparison. In addition, the expression of the remaining uncloned rice genes and their relationship with the phenotype are further analyzed. The genes of seed germination and fresh weight and the length of the hypocotyl, as well as the genes of sodium and calcium content are found to exist. Possible homologous genes.

【學(xué)位授予單位】：中國農(nóng)業(yè)科學(xué)院
【學(xué)位級別】：博士后
【學(xué)位授予年份】：2017
【分類號】：Q943.2

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