利用混池测序检测不同鸡种的全基因组结构变异

发布时间：2018-01-09 01:31

本文关键词：利用混池测序检测不同鸡种的全基因组结构变异　出处：《中国农业大学》2016年博士论文　论文类型：学位论文

【摘要】：鸡是最早被人类驯化的禽类之一,鸡蛋和鸡肉都是现代人类重要的蛋白质来源。经过漫长的进化和选择过程,鸡逐渐形成了现在丰富多样的品种。对鸡的遗传多样性和群体进化的研究有相当重要的生物学意义,多个研究表明结构变异在这些方面具有重要的作用。随着生物芯片技术以及第二代测序技术的发展,给基因组中结构变异的研究带来了极大的便利和革新。现在通常意义所指的结构变异是基因组中变异的碱基数大于50bp的变异,主要包括插入、缺失、倒位、转座和拷贝数变异。虽然结构变异的绝对数量没有单核苷酸变异以及短的插入缺失多,但是由于结构变异影响的碱基总数更多,所以对于全基因组来讲,结构变异带来的影响可能会更大。对人类的研究发现,结构变异所影响碱基总数最大可能占到人类基因组的5%。近年来,由于人们渐渐意识到结构变异对群体多样性以及重要性状等方面具有重要作用,使得结构变异的研究越来越受到广大科研工作者的广泛关注。本研究利用第二代测序技术结合基因组混池的方法,对4个具有代表性的鸡种各选择了20只鸡基因组混池之后进行全基因组混池测序。这种方法通过降低每个个体基因组的代表性,达到高效且低成本的对群体进行测序,进而获得大量的多态性信息。这4个品种分别选择了肉鸡(科宝)、蛋鸡(白来航)、中国地方鸡种(乌鸡)和原鸡品种(德宏原鸡),这样的选择保证了实验材料选择的多样性和差异性。我们利用得到的测序数据结合多种方法对全基因组的结构变异进行检测,然后通过严格的筛选和合并过程将结果进行整合得到最终的全基因组结构变异集合。检出的结构变异包括了缺失、插入、倒位和拷贝数变异等多种类型。4个品种中均检出大量的结构变异,覆盖了全基因组1.75%至2.29%的区域,其中数量最多的是缺失,最大的变异是倒位,有部分结构变异与外显子区域或者基因调控区有重叠。利用检出的结构变异,绘制了所研究品种高分辨率的全基因组结构变异图谱,我们发现基因组上结构变异的分布并不是随机的而是存在一定的分布热点。之后对各个品种的结构变异检出进行了比较,发现有4422个缺失变异在4个品种中都被检出,此外每个品种平均有近20%的结构变异是品种特有的。经过和QTL的关联、GO和KEGG分析,发现这些结构变异可能在品种的形成过程中起到了重要的作用。综上所述,本研究利用一种高效而且低成本的测序手段一混池测序对具有代表性的4个鸡种进行了全基因组结构变异的检测,并且为利用混池测序检测鸡的结构变异的提供了良好的参考。首先,利用检出结果构建了高分辨率的全基因组结构变异图谱,分析了结构变异的分布特点和可能的生物学作用。发现结构变异的分布可能跟重复序列有关系,而且SNP的分布和缺失的分布存在一定的关联性。其次,利用品种间结构变异的差异,结合遗传学和生物信息学研究手段,我们发现结构变异对科宝肉鸡的生长速度可能产生了影响,对不同品种的表型性状的差异也有一定的贡献。
[Abstract]:Chicken is one of the earliest domesticated poultry, egg and chicken are an important source of protein for modern humans. After a long process of evolution and selection of chicken, and gradually formed the rich and diverse varieties. There is very important to study the biological significance of chicken genetic diversity and population evolution, a number of studies show that structural variation has an important role in these aspects. With the development of the bio chip technology and the second generation sequencing technology, has brought great convenience to the research and innovation of structural variation in the genome. It usually refers to the significance of structural variation is the variation in the genome variation base of more than 50bp, mainly including insertion, deletion, inversion transposition, and copy number variation. Although the absolute number of structure variation and no single nucleotide variation in short insertions and deletions, but due to structural variability affects more total bases So much for the whole genome, affect the structure with the variation may be greater. The discovery of human studies, the influence of base structure variation may account for the largest number of human genome 5%. in recent years, as people gradually realized that the structure variation plays an important role on the diversity and importance of shape, which makes the research structure variation has attracted extensive attention of researchers. The research method of the second generation sequencing technology combined with genomic mixed pool, after the 4 chicken representative of each selected 20 chicken genome mixed whole genome sequencing mixed pool pool. This method by reducing the representative of each individual genome. To achieve high efficiency and low cost of sequencing groups, and then get a lot of information. The polymorphism of the 4 cultivars were selected broilers (Ke Bao), chickens (White Leghorn), China Local chicken (chicken) and fowl varieties (Dehong, gallus) this choice ensures experimental material selection diversity and difference. We use the sequencing data obtained by using various methods to detect structure variation on the whole genome, and then through the screening and merging process strictly will integrate the whole set of results obtained genomic structure variation. The final structure variation detection including deletion, insertion, inversion and copy were detected in the number of variation of structure variation and other types of.4 species, covering the area of 1.75% to 2.29% of the whole genome, which is the largest number of missing, the biggest variation is inversion, some structural variation and the explicit regulatory region of sub region or gene overlap. Using mutation detection, whole genome structural variation map of varieties of high resolution rendering, we found that the gene structure of group And the same distribution is not random but there is a distribution of hot spots. After the structure variation of each variety were compared, found that 4422 deletion mutations were detected in 4 varieties, each variety in addition average structure variation is nearly 20% varieties. The unique association and QTL analysis. GO and KEGG found the structural variation in the formation process of varieties may play an important role. In conclusion, an efficient and low cost sequencing means mixed pool sequencing of 4 chicken representative of the gene detection group structure variation in this paper, and for the use of the structure the variation of mixing pool sequencing chicken to provide a good reference. Firstly, the detection results of constructing genomic structural variation map with high resolution, analyzes the distribution characteristics of structure variation and possible biological role. Distribution structure variation may have a relationship with repeat sequence, and there is a certain correlation between the distribution and the loss of SNP. Secondly, the differences between the varieties structure variation, the combination of genetics and bioinformatics research methods, we found that the structure of the mutation rate on growth of chicken meat cobio may have had an impact, also have certain the difference of phenotypic traits of different varieties.

【学位授予单位】：中国农业大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：S831

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