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

发布时间：2018-06-21 08:42

  本文选题：非综合征型耳聋 + GJB2　； 参考：《兰州大学》2014年硕士论文

【摘要】：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mtDNA1555AG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mtDNA1555AG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(X2=8.140, P=0.043)。 c.235de1C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.35de1G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.299300delAT、 c.313326de114、 c.9GA、 c.176191de116、 C.427CT、 c.IVS1+1GA、 c.lO9GA、 c.368CA、 c.380GA。 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(X2=8.180, P=0.042)。c.919-2AG和c.2027TA是新疆地区维吾尔族耳聋患者的热点突变,c.919-2AG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.281CT、 c.589GA、c.1174AT、c.1229CT、c.1975GC、c.2168AG、c.109GT、c.147CG. c.170CA、c.387de1C、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mtDNA1555AG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(P0.05)。 结论： 1、GJB2基因、SLC26A4基因、]mtDNA1494C＞T和mtDNA1555AG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mtDNA1555AG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。
[Abstract]:Objective: to analyze the molecular epidemiology and mutation characteristics of GJB2 gene SLC26A4 gene and mtDNA1555AG and mtDNA1494C > T in patients with nonsyndromic hearing loss (NSHLL) deafness in Xinjiang minority by SNPscan method. Methods: in this study, 428cases of Uygur nationality in Xinjiang Uygur Autonomous region, 41 cases of Hui nationality, 64 cases of Kazak nationality and 32 cases of Kirgiz nationality were selected as the subjects. All patients with moderate to very severe sensorineural hearing loss were examined by SNPscan method for the known mutation sites of GJB2, SLC26A4 genes, mtDNA1555AG and mtDNA1494C > T under the condition of signing informed consent letters, extracting peripheral venous blood and semi-automatically extracting genomic DNA by magnetic bead method, and using SNPscan method to screen GJB2, SLC26A4 gene, mtDNA1555AG and mtDNA1494C > T. The mutation frequency and hot spot mutation of the above three genes in the four ethnic minorities were summarized and compared with 401 non-syndromic deafness patients in Xinjiang. Results: 1. The alleles frequency of GJB2 gene mutation in Xinjiang Uygur, Hui, Kazak and Kirgiz NSHL patients were 10.1687 / 856 / 85 / 82 / 10.16, respectively. The difference was statistically significant (X _ 2H _ 2 8.140, P _ (0.04343) C) and C. 235de1C only found in Uygur and Hui nationalities. The allele frequencies were 5.14 / 856 and 13.41 / 82, respectively. And c. 35delG was found in Uygur, Hui, Kazak and Kirgiz ethnic groups. The allele frequencies were 3.15 / 85 / 856 / 1.21 and 1 / 82 / 8.59 / 128) and 1.56% / 64 respectively. C.235delC was a hot spot mutation in Uygur and Hui deafness patients in Xinjiang. C. 35de1G was a Uygur nationality. The hot spot mutation of Kazakh and Kirgiz. Other mutation loci detected include: c.299300delAT, c.313326de114, c.9GA, c.176191de116, c.427CT, c.IVS1GA, c.lO9GA, c.368CA, c.380GA.2SLC26A4 in Uygur and Hui. The alleles frequency of pathogenic mutation loci in NSHL deafness patients of Kazak and Kirgiz were 7.71c / 856 and 13.41C / 856, respectively. The frequency of alleles was 11.82% 5.47%, 5.47%, 128% 1.56%, and the difference was statistically significant (X28.180, P0.042P .c.919-2AG and c.2027TA). It was a hot spot mutation in Uygur deafness patients in Xinjiang. C.919-2AG was a Hui nationality. The hot spot mutation of Kazakh and Kirgiz. 鍏跺畠妫，

本文编号：2047927