本文選題：基因組印跡 + 等位基因甲基化特異性�。� 參考：《大連醫(yī)科大學》2017年碩士論文

【摘要】：基因組印跡是一種十分重要的表觀遺傳學現(xiàn)象,也是DNA甲基化最為人熟知的功能之一,印跡基因的選擇性表達是由父本或母本遺傳而來,通過控制印跡基因的調控區(qū)域的甲基化來實現(xiàn)。在哺乳動物中,印跡基因從親代的兩個等位基因中選擇性表達其中的一個,從而在功能上實現(xiàn)單倍體的特征�；蚪M印跡與胎盤哺乳動物的進化相當密切的聯(lián)系,而基因組印跡缺陷與人類疾病也有著深刻的聯(lián)系。二代測序技術的進步使得DNA甲基化的研究發(fā)生了很大的變化,全基因組重亞硫酸鹽甲基化測序(WGBS),甲基化DNA免疫共沉淀測序(MeDIP-Seq),以及采用酶切方式的簡化甲基化測序(RRBS)等多種甲基化分析手段使我們從單堿基水平分析細胞甲基化。對于基因組印跡研究來說,現(xiàn)有的生物信息學分析一般需要了解親本的遺傳標記用于在子代中進行區(qū)分,通常的研究方法是將兩種不同品系的小鼠進行雜交,通過親本的單核苷酸多態(tài)性(SNP)進行父母本區(qū)分。本課題中,我們用一種新的方法來尋找等位基因特異性甲基化(ASM)區(qū)域。我們先對全基因組甲基化測序的片段進行分析,針對每個片段的甲基化狀態(tài)進行分析,將多個片段甲基化信息用卷積的方法關聯(lián)起來描述該區(qū)域甲基化狀態(tài),我們的模型雖然無法區(qū)分父母本信息,但是仍能較準確的確定出等位基因特異性甲基化區(qū)域。利用我們的模型分析了一組小鼠胚胎發(fā)育過程中不同發(fā)育時期的全基因組甲基化數(shù)據(jù),利用我們的方法對不同時期細胞的等位基因甲基化特異性區(qū)域進行篩選,與根據(jù)小鼠品系多核苷酸多態(tài)性區(qū)分得到的父母本甲基化信息進行對比,發(fā)現(xiàn)本課題使用的方法能夠較好的找到等位基因甲基化特異性區(qū)域。通過分析小鼠的等位基因甲基化特異性區(qū)域,我們發(fā)現(xiàn)在小鼠發(fā)育階段,這些區(qū)域都有較高的保守性,并且這些區(qū)域在基因組上呈現(xiàn)成簇出現(xiàn)的特征,富集出現(xiàn)在CpG高密度區(qū)域、啟動子區(qū)域。本課題中給出的方法能夠在使用在親本品系未知的情況下較準確的尋找ASM區(qū)域,從而能夠更好的利用現(xiàn)有的眾多未包含親本品系信息的甲基化測序信息中進行生物信息學研究。
[Abstract]:Genomic imprinting is a very important epigenetic phenomenon and one of the most well-known functions of DNA methylation. The selective expression of imprinted genes is inherited from male or female parents. This is achieved by controlling the methylation of the regulatory region of the imprinted gene. In mammals, the imprinted genes selectively express one of the two alleles of their parents, thus functionally realizing the haploid characteristics. Genomic imprinting is closely related to the evolution of placental mammals, and genomic imprinting defects are also closely related to human diseases. Advances in second-generation sequencing technology have led to significant changes in the study of DNA methylation. The whole genome heavy sulfite methylation sequencing (WGBS), methylated DNA immunoprecipitation sequencing (MeDIP-SeqN), and simplified methylation sequencing (RRBs) by enzyme digestion make us analyze cell methylation from single base level. For genomic imprinting studies, existing bioinformatics analysis generally requires understanding that parental genetic markers are used to distinguish between offspring, and the usual method is to cross two different strains of mice. Parental differentiation was made by single nucleotide polymorphisms (SNPs) of parents. In this study, we used a new method to find the allele-specific methylated ASM region. We first analyzed the whole genome methylation sequence fragments, analyzed the methylation status of each fragment, and associated multiple fragments methylation information with convolution method to describe the region methylation state. Although our model can not distinguish parental information, it can identify allele-specific methylation region more accurately. We used our model to analyze the whole genome methylation data of mouse embryonic development at different stages of development. We used our method to screen allelic methylation specific regions of cells at different stages. Compared with the parent methylation information based on the polynucleotide polymorphism of mouse strain, it was found that the method used in this study could better find the specific region of allele methylation. By analyzing the specific regions of allelic methylation in mice, we found that these regions were highly conserved during the development of mice, and these regions appeared in clusters on the genome. Enrichment occurs in the high density region of CpG and in the promoter region. The method presented in this paper can be used to find the ASM region more accurately in the case of parents unknown, so that the bioinformatics can be better used in the existing methylation sequencing information which does not contain parental information.
【學位授予單位】：大連醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：Q78

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1 陳成軍;基于Tagmeth檢測等位基因特異性甲基化的方法[D];大連醫(yī)科大學;2017年

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本文編號：1809907