中国南方沿海及北方内陆食管癌高发区人群的遗传背景研究—来自Y染色体的证据
发布时间：2018-07-25 06:19
【摘要】：背景 位于中国沿海的潮汕及福建闽南地区和位于北方内陆的太行山区,地理位置上相距较远,生活环境迥异,却同为我国的食管癌(Esophageal cancer,EC)高发区,而且具有相似的恶性肿瘤谱。据历史记载,现在潮汕人群的祖先大多为中原内陆居民(河南和山西)途径福建省迁移而来的。语言,家谱,碑文及考古发现也支持这一史实,因此本文提出一假设即潮汕食管癌高危人群与其它两个高危人群具有相似的遗传背景,他们可能来源于一较近的共同祖先,正是由于这种相近的遗传结构,导致了他们共同的食管癌易感性。 目的 获取太行山区、福建闽南及潮汕地区食管癌高危人群和潮汕地区食管癌人群的Y染色体DNA多态性信息,为本文的假设提供来自父系的遗传学证据。同时为这三个地区人群的个体识别提供参考资料,丰富这些地区的Y染色体单核苷酸多态性(single nucleotide polymorphism, SNP)及短串联重复序列(short tandem repeat, STR)数据库。方法 1.选取16个具有东亚人群特异性的Y-SNP及7个Y-STR位点进行研究。用三种方法进行分型,对没有长度变化的SNP标记,用限制性片段长度多态性(Restriction Fragment Length Polymorphism, RFLP)检测;对有长度变化的SNP及7个STR位点先进行荧光PCR扩增,再上基因分析仪进行电泳分型;对于M1,可直接利用琼脂糖凝胶电泳分型。 2.根据每个个体所有SNP分型结果及Y染色体国际命名委员会的命名原则,确定每个个体的单体群,分析它们在四个研究人群中的频率分布并进行卡方检验。直接计算SNP基因型及单体群多态性,并进行主成分分析、相关分析及分层聚类分析。 3.根据每个个体7个Y-STR的分型结果,计算STR基因型及单体型频率、基因型及单体型多态性。与比对资料一起进行主成分、相关及分层聚类分析,利用Arlequin3.0软件计算群体间的遗传距离,然后再用Mega2.1软件构建邻接法(Neighbor-joining Method,NJ)系统发育树。绘制O2a*及O3e1单体群的网络结构图。 结果 1. O3*、O3e*及O3e1*单体群均具有M122突变,它们的合计频率在太行山区、福建及潮汕地区食管癌高危人群中分别为60.42%、66.22%及65.16%,是三个高危人群的主要单体群,卡方检验提示它们间的频率差别无统计学意义。潮汕地区食管癌人群这三个单体群的频率也较高,合计频率为36.67%,与三个高危人群不同的是它同时具有较高频率的O2a*单体群(30.0%)。 2.抽取四个研究人群及东亚5个不同语系人群主成分分析的前两个主成分值,构建主成分散点图,结果显示三个高危人群均位于图的最右侧,即汉藏人群分布最密集的地方。相关分析发现正是汉藏人群的特征单体群O3e*与汉藏人群的分布趋势相吻合。 3. Y-SNP及Y-STR主成分及分层聚类分析显示三个高危人群及潮汕地区食管癌人群聚在一起,相关分析表明三个食管癌高危人群之间呈显著正相关,另外潮汕地区食管癌与太行山区食管癌高危人群间也呈显著正相关关系。 4.遗传距离分析显示太行山区、福建及潮汕食管癌高危人群间关系较近,这种亲缘关系在N-J邻接树中得到进一步的反映。 5. O2a*单体群网络结构图示,与东亚其他人群比较,本研究的18个O2a*个体紧密聚在一起,位于网络图外围的一个分支上。O3e1单体群网络结构图示在中心节点及次中心节点均有四个人群的个体分布,它们具有相同的Y-STR突变。 6.除四个研究人群的DYS391及潮汕食管癌人群的DYS389I位点的基因多态性小于0.5外,四个人群在其它Y-STR位点的基因多样性均大于0.5。另外四个人群7个Y-STR单体型多样性均在0.980以上。 结论 1.父系遗传结构研究结果提示河南太行山区、福建及潮汕高危人群均属于典型的汉藏人群,它们之间具有较近的亲缘关系,可能来自一较近的共同祖先。 2.潮汕地区食管癌人群与三个食管癌高危人群也存在较近亲缘关系,但其祖先可能与百越人群具有更多的基因交流。食管癌在潮汕高危人群中可能不是随机发生的,O2a*单倍群可能是筛选潮汕食管癌易感人群有用的候选标记。 3. 7个Y-STR在四个人群中具有丰富的遗传多态性,由这些位点组成的Y-STR单体型有很高的个体识别率,具有重要的法医学应用价值。
[Abstract]:background
In Chaoshan, Fujian, south of Fujian and the Taihang Mountains in the northern inland of China, the geographical location is far away and the living environment is very different, but it is the high incidence area of Esophageal cancer (EC) in China, and it has a similar malignant tumor spectrum. Henan and Shanxi, which were migrated through Fujian Province, supported this history by language, family genealogy, inscriptions, and archaeological discoveries. Therefore, this article hypothesized that the high risk population in Chaoshan esophagus cancer has a similar genetic background to the other two high-risk groups, which may come from a closer common ancestor, which is due to this similar genetic knot. They cause their common susceptibility to esophageal cancer.
objective
The Y chromosome DNA polymorphism information of the high risk population of esophageal cancer in Taihang Mountains and Chaozhou and Chaoshan area, Fujian, and the esophagus cancer population in Chaoshan region, provides genetic evidence from paternal origin for this hypothesis, and provides reference for individual identification in these three regions to enrich the single nucleotide polymorphisms of Y chromosomes in these areas. Sex (single nucleotide polymorphism, SNP) and short tandem repeat (STR) databases.
1. Y-SNP and 7 Y-STR loci, which were specific to East Asian population, were studied. Three methods were used for typing, SNP markers without length change, restriction fragment length polymorphism (Restriction Fragment Length Polymorphism, RFLP), and PCR amplification of SNP and 7 STR loci with length change, and then PCR amplification. For M1, agarose gel electrophoresis can be used directly.
2. according to the SNP typing results of each individual and the naming principle of the Y chromosome international naming Committee, the single body group of each individual was determined, the frequency distribution in the four subjects was analyzed and the chi square test was carried out. The SNP genotype and the single body polymorphism were calculated directly, and the principal component analysis, the correlation analysis and the stratified cluster analysis were performed.
3. according to the classification results of 7 Y-STR for each individual, the STR genotype and haplotype frequency, genotype and haplotype polymorphism were calculated, and the correlation and stratified cluster analysis were carried out with the comparison data. The genetic distance between groups was calculated by Arlequin3.0 software, and then the adjacency method was constructed by Mega2.1 software (Neighbor-joining Method, NJ). (2) phylogenetic tree. The network structure of O2 a * and O 3E 1 monomer groups is plotted.
Result
1. O3*, O3e* and O3e1* monomers all have M122 mutation. Their total frequency is in Taihang mountain area. The high risk population of esophageal cancer in Fujian and Chaoshan region is 60.42%, 66.22% and 65.16%, respectively. It is the main single body of three high-risk groups. The chi square test suggests that there is no statistical difference between them. The three of the esophageal cancer population in Chaoshan region The frequency of the monomer group was also higher, with a total frequency of 36.67%. Unlike the three high-risk groups, it also had a high frequency of O2 a * monomer group (30.0%).
2. the score of the first two main components of the principal component analysis of four people and 5 different languages in East Asia was constructed. The results showed that the three high-risk groups were all located on the right side of the map, that is, the densest distribution of the Han and Tibetan populations. The correlation analysis found that the distribution of the O3e* and the Han population in the Han and Tibetan populations was the distribution of the population of the Han and Tibetan populations. The trend coincides.
3. Y-SNP and Y-STR principal components and stratified cluster analysis showed that three high-risk groups and Chaoshan esophageal cancer population were gathered together. Correlation analysis showed that there was a significant positive correlation between three high-risk groups of esophageal cancer, and there was a significant positive correlation between esophageal cancer in Chaozhou and Taihang Mountains and high risk population of esophageal cancer in Taihang mountain area.
4. genetic distance analysis showed that the relationship between the high-risk population of Fujian and Chaoshan esophageal cancer was close. This relationship was further reflected in the N-J adjacent tree.
5. O2a* mono network structure diagram shows that 18 O2a* individuals in this study are closely together compared with other East Asian populations. The network structure of.O3e1 mono on a branch of the network map shows the individual distribution of four people in the central node and the sub center node, and they have the same Y-STR mutation.
6. the gene polymorphism of DYS389I loci in DYS391 and Chaoshan esophageal cancer population in four subjects was less than 0.5, and the genetic diversity of four population at other Y-STR loci was greater than that of the other four groups of 0.5. and 7 Y-STR haplotype diversity of more than 0.980.
conclusion
The results of the study of 1. paternal genetic structure suggest that Henan Taihang Mountains, Fujian and Chaoshan high risk population belong to the typical Han population, and they have close relationship between them, which may come from a closer common ancestor.
2. the population of esophageal cancer in Chaozhou and Shantou area is also closely related to the high risk population of three esophageal cancer, but its ancestors may have more genetic communication with the Baiyue population. The esophageal cancer may not occur at random in the high risk population in Chaoshan. The O2a* haploid group may be a useful candidate marker for screening the susceptible population of Chaoshan esophagus cancer.
The 3.7 Y-STR has a rich genetic polymorphism among the four populations. The Y-STR haplotype composed of these sites has a high individual recognition rate, which has important forensic application value.
【学位授予单位】：汕头大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R735.1;R394;D919
[Abstract]:background
In Chaoshan, Fujian, south of Fujian and the Taihang Mountains in the northern inland of China, the geographical location is far away and the living environment is very different, but it is the high incidence area of Esophageal cancer (EC) in China, and it has a similar malignant tumor spectrum. Henan and Shanxi, which were migrated through Fujian Province, supported this history by language, family genealogy, inscriptions, and archaeological discoveries. Therefore, this article hypothesized that the high risk population in Chaoshan esophagus cancer has a similar genetic background to the other two high-risk groups, which may come from a closer common ancestor, which is due to this similar genetic knot. They cause their common susceptibility to esophageal cancer.
objective
The Y chromosome DNA polymorphism information of the high risk population of esophageal cancer in Taihang Mountains and Chaozhou and Chaoshan area, Fujian, and the esophagus cancer population in Chaoshan region, provides genetic evidence from paternal origin for this hypothesis, and provides reference for individual identification in these three regions to enrich the single nucleotide polymorphisms of Y chromosomes in these areas. Sex (single nucleotide polymorphism, SNP) and short tandem repeat (STR) databases.
1. Y-SNP and 7 Y-STR loci, which were specific to East Asian population, were studied. Three methods were used for typing, SNP markers without length change, restriction fragment length polymorphism (Restriction Fragment Length Polymorphism, RFLP), and PCR amplification of SNP and 7 STR loci with length change, and then PCR amplification. For M1, agarose gel electrophoresis can be used directly.
2. according to the SNP typing results of each individual and the naming principle of the Y chromosome international naming Committee, the single body group of each individual was determined, the frequency distribution in the four subjects was analyzed and the chi square test was carried out. The SNP genotype and the single body polymorphism were calculated directly, and the principal component analysis, the correlation analysis and the stratified cluster analysis were performed.
3. according to the classification results of 7 Y-STR for each individual, the STR genotype and haplotype frequency, genotype and haplotype polymorphism were calculated, and the correlation and stratified cluster analysis were carried out with the comparison data. The genetic distance between groups was calculated by Arlequin3.0 software, and then the adjacency method was constructed by Mega2.1 software (Neighbor-joining Method, NJ). (2) phylogenetic tree. The network structure of O2 a * and O 3E 1 monomer groups is plotted.
Result
1. O3*, O3e* and O3e1* monomers all have M122 mutation. Their total frequency is in Taihang mountain area. The high risk population of esophageal cancer in Fujian and Chaoshan region is 60.42%, 66.22% and 65.16%, respectively. It is the main single body of three high-risk groups. The chi square test suggests that there is no statistical difference between them. The three of the esophageal cancer population in Chaoshan region The frequency of the monomer group was also higher, with a total frequency of 36.67%. Unlike the three high-risk groups, it also had a high frequency of O2 a * monomer group (30.0%).
2. the score of the first two main components of the principal component analysis of four people and 5 different languages in East Asia was constructed. The results showed that the three high-risk groups were all located on the right side of the map, that is, the densest distribution of the Han and Tibetan populations. The correlation analysis found that the distribution of the O3e* and the Han population in the Han and Tibetan populations was the distribution of the population of the Han and Tibetan populations. The trend coincides.
3. Y-SNP and Y-STR principal components and stratified cluster analysis showed that three high-risk groups and Chaoshan esophageal cancer population were gathered together. Correlation analysis showed that there was a significant positive correlation between three high-risk groups of esophageal cancer, and there was a significant positive correlation between esophageal cancer in Chaozhou and Taihang Mountains and high risk population of esophageal cancer in Taihang mountain area.
4. genetic distance analysis showed that the relationship between the high-risk population of Fujian and Chaoshan esophageal cancer was close. This relationship was further reflected in the N-J adjacent tree.
5. O2a* mono network structure diagram shows that 18 O2a* individuals in this study are closely together compared with other East Asian populations. The network structure of.O3e1 mono on a branch of the network map shows the individual distribution of four people in the central node and the sub center node, and they have the same Y-STR mutation.
6. the gene polymorphism of DYS389I loci in DYS391 and Chaoshan esophageal cancer population in four subjects was less than 0.5, and the genetic diversity of four population at other Y-STR loci was greater than that of the other four groups of 0.5. and 7 Y-STR haplotype diversity of more than 0.980.
conclusion
The results of the study of 1. paternal genetic structure suggest that Henan Taihang Mountains, Fujian and Chaoshan high risk population belong to the typical Han population, and they have close relationship between them, which may come from a closer common ancestor.
2. the population of esophageal cancer in Chaozhou and Shantou area is also closely related to the high risk population of three esophageal cancer, but its ancestors may have more genetic communication with the Baiyue population. The esophageal cancer may not occur at random in the high risk population in Chaoshan. The O2a* haploid group may be a useful candidate marker for screening the susceptible population of Chaoshan esophagus cancer.
The 3.7 Y-STR has a rich genetic polymorphism among the four populations. The Y-STR haplotype composed of these sites has a high individual recognition rate, which has important forensic application value.
【学位授予单位】：汕头大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R735.1;R394;D919
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