中國南方沿海及北方內(nèi)陸食管癌高發(fā)區(qū)人群的遺傳背景研究—來自Y染色體的證據(jù)
發(fā)布時間：2018-07-25 06:19
【摘要】：背景 位于中國沿海的潮汕及福建閩南地區(qū)和位于北方內(nèi)陸的太行山區(qū),地理位置上相距較遠(yuǎn),生活環(huán)境迥異,卻同為我國的食管癌(Esophageal cancer,EC)高發(fā)區(qū),而且具有相似的惡性腫瘤譜。據(jù)歷史記載,現(xiàn)在潮汕人群的祖先大多為中原內(nèi)陸居民(河南和山西)途徑福建省遷移而來的。語言,家譜,碑文及考古發(fā)現(xiàn)也支持這一史實,因此本文提出一假設(shè)即潮汕食管癌高危人群與其它兩個高危人群具有相似的遺傳背景,他們可能來源于一較近的共同祖先,正是由于這種相近的遺傳結(jié)構(gòu),導(dǎo)致了他們共同的食管癌易感性。 目的 獲取太行山區(qū)、福建閩南及潮汕地區(qū)食管癌高危人群和潮汕地區(qū)食管癌人群的Y染色體DNA多態(tài)性信息,為本文的假設(shè)提供來自父系的遺傳學(xué)證據(jù)。同時為這三個地區(qū)人群的個體識別提供參考資料,豐富這些地區(qū)的Y染色體單核苷酸多態(tài)性(single nucleotide polymorphism, SNP)及短串聯(lián)重復(fù)序列(short tandem repeat, STR)數(shù)據(jù)庫。方法 1.選取16個具有東亞人群特異性的Y-SNP及7個Y-STR位點進(jìn)行研究。用三種方法進(jìn)行分型,對沒有長度變化的SNP標(biāo)記,用限制性片段長度多態(tài)性(Restriction Fragment Length Polymorphism, RFLP)檢測;對有長度變化的SNP及7個STR位點先進(jìn)行熒光PCR擴(kuò)增,再上基因分析儀進(jìn)行電泳分型;對于M1,可直接利用瓊脂糖凝膠電泳分型。 2.根據(jù)每個個體所有SNP分型結(jié)果及Y染色體國際命名委員會的命名原則,確定每個個體的單體群,分析它們在四個研究人群中的頻率分布并進(jìn)行卡方檢驗。直接計算SNP基因型及單體群多態(tài)性,并進(jìn)行主成分分析、相關(guān)分析及分層聚類分析。 3.根據(jù)每個個體7個Y-STR的分型結(jié)果,計算STR基因型及單體型頻率、基因型及單體型多態(tài)性。與比對資料一起進(jìn)行主成分、相關(guān)及分層聚類分析,利用Arlequin3.0軟件計算群體間的遺傳距離,然后再用Mega2.1軟件構(gòu)建鄰接法(Neighbor-joining Method,NJ)系統(tǒng)發(fā)育樹。繪制O2a*及O3e1單體群的網(wǎng)絡(luò)結(jié)構(gòu)圖。 結(jié)果 1. O3*、O3e*及O3e1*單體群均具有M122突變,它們的合計頻率在太行山區(qū)、福建及潮汕地區(qū)食管癌高危人群中分別為60.42%、66.22%及65.16%,是三個高危人群的主要單體群,卡方檢驗提示它們間的頻率差別無統(tǒng)計學(xué)意義。潮汕地區(qū)食管癌人群這三個單體群的頻率也較高,合計頻率為36.67%,與三個高危人群不同的是它同時具有較高頻率的O2a*單體群(30.0%)。 2.抽取四個研究人群及東亞5個不同語系人群主成分分析的前兩個主成分值,構(gòu)建主成分散點圖,結(jié)果顯示三個高危人群均位于圖的最右側(cè),即漢藏人群分布最密集的地方。相關(guān)分析發(fā)現(xiàn)正是漢藏人群的特征單體群O3e*與漢藏人群的分布趨勢相吻合。 3. Y-SNP及Y-STR主成分及分層聚類分析顯示三個高危人群及潮汕地區(qū)食管癌人群聚在一起,相關(guān)分析表明三個食管癌高危人群之間呈顯著正相關(guān),另外潮汕地區(qū)食管癌與太行山區(qū)食管癌高危人群間也呈顯著正相關(guān)關(guān)系。 4.遺傳距離分析顯示太行山區(qū)、福建及潮汕食管癌高危人群間關(guān)系較近,這種親緣關(guān)系在N-J鄰接樹中得到進(jìn)一步的反映。 5. O2a*單體群網(wǎng)絡(luò)結(jié)構(gòu)圖示,與東亞其他人群比較,本研究的18個O2a*個體緊密聚在一起,位于網(wǎng)絡(luò)圖外圍的一個分支上。O3e1單體群網(wǎng)絡(luò)結(jié)構(gòu)圖示在中心節(jié)點及次中心節(jié)點均有四個人群的個體分布,它們具有相同的Y-STR突變。 6.除四個研究人群的DYS391及潮汕食管癌人群的DYS389I位點的基因多態(tài)性小于0.5外,四個人群在其它Y-STR位點的基因多樣性均大于0.5。另外四個人群7個Y-STR單體型多樣性均在0.980以上。 結(jié)論 1.父系遺傳結(jié)構(gòu)研究結(jié)果提示河南太行山區(qū)、福建及潮汕高危人群均屬于典型的漢藏人群,它們之間具有較近的親緣關(guān)系,可能來自一較近的共同祖先。 2.潮汕地區(qū)食管癌人群與三個食管癌高危人群也存在較近親緣關(guān)系,但其祖先可能與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隨機(jī)發(fā)生的,O2a*單倍群可能是篩選潮汕食管癌易感人群有用的候選標(biāo)記。 3. 7個Y-STR在四個人群中具有豐富的遺傳多態(tài)性,由這些位點組成的Y-STR單體型有很高的個體識別率,具有重要的法醫(yī)學(xué)應(yīng)用價值。
[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.
【學(xué)位授予單位】：汕頭大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：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.
【學(xué)位授予單位】：汕頭大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R735.1;R394;D919
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