本文選題：非綜合征型耳聾 + GJB2　； 參考：《蘭州大學(xué)》2014年碩士論文

【摘要】：目的：用SNPscan法對(duì)新疆主要少數(shù)民族非綜合征型(nonsydromic hearing loss, NSHL)耳聾患者進(jìn)行GJB2基因、SLC26A4基因突變及mtDNA1555AG和mtDNA1494C＞T的分子流行病學(xué)及突變特征分析。 方法：本課題選取新疆維吾爾自治區(qū)維吾爾族(428例)、回族(41例)、哈薩克族(64例)、柯?tīng)柨俗巫?32例)四個(gè)主要少數(shù)民族565例NSHL患者為研究對(duì)象,均為中度至極重度感音神經(jīng)性聾患者,在簽署知情同意書(shū)的前提下,抽取外周靜脈血,磁珠法半自動(dòng)提取基因組DNA,用SNPscan方法對(duì)GJB2、 SLC26A4基因已知突變位點(diǎn)及mtDNA1555AG和mtDNA1494C＞T進(jìn)行篩查,總結(jié)上述三個(gè)基因在四個(gè)少數(shù)民族中的突變頻率和熱點(diǎn)突變情況,并與課題組已經(jīng)完成的新疆地區(qū)401例非綜合癥型耳聾患者從檢測(cè)方法、突變特征上進(jìn)行比較分析。 結(jié)果： 1、新疆維吾爾族、回族、哈薩克族和柯?tīng)柨俗巫錘SHL患者GJB2基因的致病突變位點(diǎn)等位基因頻率分別為10.16%(87/856)、15.85%(13/82)、10.16%(13/128)、1.56%(1/64),差別有統(tǒng)計(jì)學(xué)意義(X2=8.140, P=0.043)。 c.235de1C僅在維吾爾族和回族中發(fā)現(xiàn),等位基因頻率分別為5.14%(44/856)和13.41%(11/82)。而c.35delG在維吾爾族、回族、哈薩克族、柯?tīng)柨俗巫逯芯邪l(fā)現(xiàn),等位基因頻率分別為3.15%(27/856)、1.21%(1/82)、8.59%(11/128)和1.56%(1/64). c.235delC是新疆地區(qū)維吾爾族和回族耳聾患者的熱點(diǎn)突變,c.35de1G是維吾爾族、哈薩克族和柯?tīng)柨俗巫宓臒狳c(diǎn)突變。其它檢測(cè)出的突變位點(diǎn)包括：c.299300delAT、 c.313326de114、 c.9GA、 c.176191de116、 C.427CT、 c.IVS1+1GA、 c.lO9GA、 c.368CA、 c.380GA。 2、 SLC26A4基因在維吾爾族、回族、哈薩克族和柯?tīng)柨俗巫錘SHL耳聾患者中的致病突變位點(diǎn)等位基因頻率分別為7.71%(66/856)、13.41%(11/82)、5.47%(7/128)、1.56%(1/64),差別有統(tǒng)計(jì)學(xué)意義(X2=8.180, P=0.042)。c.919-2AG和c.2027TA是新疆地區(qū)維吾爾族耳聾患者的熱點(diǎn)突變,c.919-2AG是回族、哈薩克族和柯?tīng)柨俗巫宓臒狳c(diǎn)突變。其它檢測(cè)出的突變位點(diǎn)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、在維吾爾族、回族、哈薩克族和柯?tīng)柨俗巫錘SHL耳聾患者中mtDNA1555AG突變頻率分別為2.34%(10/428)、2.44%(1/41)、1.56%(1/64)、0(0/32)各民族間的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論： 1、GJB2基因、SLC26A4基因、]mtDNA1494C＞T和mtDNA1555AG在新疆維吾爾族、回族、哈薩克族、柯?tīng)柨俗巫錘SHL患者中的突變圖譜具有一定差異,具有其民族特異性。 2、 SNPscan能成功對(duì)GJB2、SLC26A4基因常見(jiàn)突變及mtDNA1494C＞T和mtDNA1555AG的SNP位點(diǎn)成功分型,且能在一個(gè)檢測(cè)流程中同時(shí)對(duì)多個(gè)突變位點(diǎn)進(jìn)行檢測(cè),是一種適合新疆少數(shù)民族常見(jiàn)耳聾基因篩查的基因檢測(cè)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. 鍏跺畠媯，

本文編號(hào)：2047927