乙型肝炎病毒C2、C1、B2基因型中SSR的比较分析

发布时间：2018-07-28 19:51

【摘要】：简单重复序列(Simple sequence repeat，SSR)普遍存在于真核生物和原核生物的基因组序列中，以前SSR被认为是基因序列中的“junk DNA”，不具有生物学功能，然而，随着研究的深入发现，SSR的突变率很高，且具有非常重要的生物功能，目前已发现的弗里德赖希共济失调等20多种疾病均是由SSR在DNA序列中扩增造成的。乙型肝炎病毒(Hepatitis B virus，HBV)是目前已知的感染人类最小的双链DNA病毒，它能够引发急慢性肝炎，同时也会显著地提高肝硬化、细胞性肝癌等重症肝病的发生率。HBV具有非常高的突变率，根据HBV-DNA的异质性，将HBV分为八种基因型(A-H)和多种基因亚型，研究表明，不同的基因型/基因亚型在地理分布、致病性、DNA序列突变、对药物治疗反应等方面均存在差异性，，目前发现C2基因亚型的致癌性最强，C1基因亚型次之，B2基因亚型再次之。HBV的基因型/基因亚型为研究SSR在基因序列中的变异、进化和功能提供了很好的条件。本论文以C2、C1、B2基因序列为材料，分析SSR在C2、C1、B2基因序列中分布的特点。结果显示，四型SSR、五型SSR、六型SSR并没有在分析的序列中出现，然而，一型SSR、二型SSR、三型SSR在每条分析的序列中均有出现，但其重复次数比较小和序列长度比较短，以上结果可能与HBV-DNA序列非常短和其突变率非常高有关；一型SSR (A)n和(T)n在序列中的含量远比(G)n和(C)n在序列中的含量高；二型SSR (TG)n和(AC)n在B2基因序列中的含量远大于其在C2、C1中的含量，(CT)n是此三种基因序列中最普遍的二型SSR，(AG)n和(TA)n在C2、C1、B2基因序列的含量比较相似；总体上分析发现，与B2基因亚型相比，二型SSR在C2和C1中的分布更相似；(AGA)n和(CCT)n在基因序列中的含量最丰富，且其在各序列间的波动最小，除(AGA)n和(CCT)n外的其它的三型SSR在序列中的含量非常少且波动性较大。总体上，一型SSR在序列中的分布按照C2、C1、B2的顺序减少；二型SSR和总的SSR在序列中的分布是按照C2、C1、B2的顺序增加的；然而，三型SSR在基因组序列中的分布与C2、C1、B2的顺序之间没有明显的相关性。
[Abstract]:Simple sequence repeat (SSR) is commonly found in the genome sequences of eukaryotes and prokaryotes. Previously, SSR was considered to be "junk DNA" in the sequence of genes and did not have biological functions. However, with the in-depth discovery of the research, the mutation rate of SSR is very high and has very important biological functions. At present, it has been found to have been found. More than 20 diseases, such as Fredrich ataxia, are caused by the amplification of SSR in the DNA sequence. Hepatitis B virus (HBV) is currently known to be the smallest double stranded DNA virus, which can cause acute and chronic hepatitis and also significantly increase the incidence of liver cirrhosis, hepatocellular carcinoma, and severe liver disease,.HB V has a very high mutation rate. According to the heterogeneity of HBV-DNA, HBV is divided into eight genotypes (A-H) and a variety of gene subtypes. The study shows that different genotypes / genotypes have differences in geographical distribution, pathogenicity, DNA sequence mutation, and drug treatment response, and the C2 gene subtype has the strongest carcinogenicity, and the C1 gene is found. The Subgenotype of genotype B2 /.HBV genotype / genotype is a good condition to study the variation, evolution and function of SSR in the gene sequence.
In this paper, C2, C1, B2 gene sequences were used as materials to analyze the characteristics of SSR distribution in the C2, C1, B2 gene sequences. The results showed that type four SSR, type five SSR, and type six SSR did not appear in the sequence of analysis. However, a type SSR, type two SSR, and three types appeared in each analysis sequence, but the number of repetitions was smaller and the sequence length was shorter. The above results may be related to the very short sequence of HBV-DNA and the very high mutation rate; the content of SSR (A) n and (T) n in the sequence is far higher than that of (G) n and (C) n in the sequence; the content of the two type SSR (TG) and N is far greater than its content in the sequence, which is the most common two type of the sequence of these three genes. SR, (AG) n and (TA) n in the C2, C1, B2 gene sequences are similar; overall analysis found that the distribution of type two SSR in C2 and C1 is more similar than that of the B2 subtype; In general, the distribution of type 1 SSR in the sequence is reduced in order of C2, C1, B2, and the distribution of type two SSR and total SSR in sequence is increased in the order of C2, C1, B2; however, there is no significant correlation between the distribution of the type three SSR in the sequence of the genome and the order of C1, and the sequence.
【学位授予单位】：湖南大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R373

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