| SNPscan法对新疆主要少数民族非综合征型耳聋患者常见聋病基因的突变特征研究分析 |
| Alternative Title | Common deafness gene characteristics analysis using SNPscan method among non-syndrome type deafness patients from the major minority nationalities in xinjiang
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| 陈兴健 |
| Thesis Advisor | 郭玉芬
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| 2014-05-23
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| Degree Grantor | 兰州大学
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| Place of Conferral | 兰州
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| Degree Name | 硕士
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| Keyword | 非综合征型耳聋
GJB2
SLC26A4
mtDNA
维吾尔族
回族
哈萨克族
柯尔克孜族
新疆
SNP
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| Abstract | 目的：用SNPscan法对新疆主要少数民族非综合征型（nonsydromic hearing loss, NSHL）耳聋患者进行GJB2基因、SLC26A4基因突变及mtDNA1555A>G和mtDNA1494C>T的分子流行病学及突变特征分析。
方法:本课题选取新疆维吾尔自治区维吾尔族（428例）、回族（41例）、哈萨克族（64例）、柯尔克孜族（32例）四个主要少数民族565例NSHL患者为研究对象，均为中度至极重度感音神经性聋患者，在签署知情同意书的前提下，抽取外周静脉血，磁珠法半自动提取基因组DNA，用SNPscan方法对GJB2、SLC26A4基因已知突变位点及mtDNA1555A>G和mtDNA1494C>T进行筛查，总结上述三个基因在四个少数民族中的突变频率和热点突变情况，并与课题组已经完成的新疆地区401例非综合症型耳聋患者从检测方法、突变特征上进行比较分析。
结果：
1、新疆维吾尔族、回族、哈萨克族和柯尔克孜族NSHL患者GJB2基因的致病突变位点等位基因频率分别为10.16%（87/856）、15.85%（13/82）、10.16%（13/128）、1.56%（1/64），差别有统计学意义（χ2 ＝8.140，P＝0.043）。c.235delC仅在维吾尔族和回族中发现，等位基因频率分别为5.14%（44/856）和13.41%（11/82）。而c.35delG在维吾尔族、回族、哈萨克族、柯尔克孜族中均有发现，等位基因频率分别为3.15%（27/856）、1.21%（1/82）、8.59%（11 /128）和1.56%（1/64）。c.235delC是新疆地区维吾尔族和回族耳聋患者的热点突变，c.35delG是维吾尔族、哈萨克族和柯尔克孜族的热点突变。其它检测出的突变位点包括： c.299_300delAT、c.313_326del14、c.9G>A、c.176_191del16、c.427C>T、c.IVS1+1G>A、c.109G>A、c.368C>A、c.380G>A。
2、SLC26A4基因在维吾尔族、回族、哈萨克族和柯尔克孜族NSHL耳聋患者中的致病突变位点等位基因频率分别为7.71%（66/856）、13.41%（11/82）、5.47%（7/128）、1.56%（1/64），差别有统计学意义（χ2 ＝8.180，P＝0.042）。c.919 -2A>G和c.2027T>A是新疆地区维吾尔族耳聋患者的热点突变，c.919 -2A>G是回族、哈萨克族和柯尔克孜族的热点突变。其它检测出的突变位点包括：c.281C>T 、c.589G>A、c.1174A>T、c.1229C>T、c.1975G>C、c.2168A>G、c.109G>T、c.147C>G、c.170C>A、c.387delC、c.1343C>T和c.2162C>T。
3、在维吾尔族、回族、哈萨克族和柯尔克孜族NSHL耳聋患者中mtDNA1555A>G突变频率分别为2.34%（10/428）、2.44%(1/41)、1.56%(1/64)、0（0/32）各民族间的差异无统计学意义（P>0.05）。
结论：
1、GJB2基因、SLC26A4基因、mtDNA1494C>T和mtDNA1555A>G在新疆维吾尔族、回族、哈萨克族、柯尔克孜族NSHL患者中的突变图谱具有一定差异，具有其民族特异性。
2、SNPscan能成功对GJB2、SLC26A4基因常见突变及mtDNA1494C>T和mtDNA1555A>G的SNP位点成功分型，且能在一个检测流程中同时对多个突变位点进行检测，是一种适合新疆少数民族常见耳聋基因筛查的基因检测方法。
关键词：非综合征型耳聋，GJB2，SLC26A4，mtDNA，维吾尔族，回族，哈萨克族，柯尔克孜族，新疆，突变，SNP |
| Other Abstract | Objective To investigate the prevalence and characteristics of Common deafness gene mutations using SNPscan method in Uygur, Hui, Kazak and Kirgiz nationalities patients with non-syndromic hearing loss(NSHL) from Xinjiang Uygur Autonomous Region of China.
Methods We collected 565 patients with moderately severe to profound sensorineural hearing loss,including Uygur, Hui, Kazak and Kirgiz nationalities, from 12 cities of Xinjiang. After informed consent was signed, peripheral blood samples were obtained to extract genomic DNA. Common pathogenic GJB2 gene, SLC26A4 gene and mtDNA gene mutations were detected by using SNPscan classification technology, followed by statistical analysis. The mutation frequencies of above three genes and hot spot mutations in various nationalities were studied. The results were compared with our previous study which has done in 401 NSHL patients from Xinjiang Uygur Autonomous Region from the test method of mutation characteristics.
Results
1.The mutated allele frequency of GJB2 in Uygur, Hui, Kazak and Kirgiz nationalities NSHL patients were 10.16%(87/856), 15.85%(13/82), 10.16%(13/128) and 1.56%(1/64), respectively. And these difference is statistically significant(χ2＝8.140，P＝0.043). The commonest mutation in Chinese deaf population c. 235delc was just found in the uygur and hui, the allele frequency of 5.14%(44/856) and 13.41%(11/82), respectively. And c.35delG was found in Uyhur,hui kazak and kirgiz , allele frequencies were 3.15% (27/856), 1.21% (1/82), 8.59% (11/128) and 1.56% (1/64). c.235delC were mutation hot spot in Uygur and Hui NSHL patients,and c.35delG were mutation hot spot in in Uygur, Kazak and Kirgiz nationalities NSHL patients. Other mutations found in GJB2 were c.299_300delAT、c.313_326del14、c.9G>A、c.176_191del16、c.427C>T、c.IVS1+1G>A、c.109G>A、c.368C>A and c.380G>A .
2.The pathogenic mutated allele frequency of SLC26A4 gene in Uygur, Hui, Kazak and Kirgiz nationalities NSHL patients were 7.71%（66/856）,13.41%（11/82）,5.47%（7/128）and 1.56%（1/64）,respectively. And these difference is statistically significant(χ2＝8.180，P＝0.042). c.919 -2A>G and c.2027T>A were mutation hot spot in Uygur nationalities NSHL patients, and c.919 -2A>G were mutation hot spot in Hui, Kazak and Kirgiz nationalities NSHL patients. Other mutations found in SLC26A4 were c.281C>T 、c.589G>A、c.1174A>T、c.1229C>T、c.1975G>C、c.2168A>G、c.109G>T、c.147C>G、c.170C>A、c.387delC、c.1343C>T and c.2162C>T.
3. The mutation ... |
| URL | 查看原文
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| Language | 中文
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| Document Type | 学位论文
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| Identifier | https://ir.lzu.edu.cn/handle/262010/223925
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| Collection | 学院待认领
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| Affiliation | 临床医学院
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Recommended Citation
GB/T 7714 |
陈兴健. SNPscan法对新疆主要少数民族非综合征型耳聋患者常见聋病基因的突变特征研究分析[D]. 兰州. 兰州大学,2014.
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