本文選題：GJB2基因 + SLC26A4基因��； 參考：《新疆醫(yī)科大學(xué)》2011年博士論文

【摘要】：目的：50%兒童期耳聾被認為與遺傳因素有關(guān),至今,與非綜合征性耳聾相關(guān)的基因共有62個已被確認,在被發(fā)現(xiàn)的眾多耳聾基因中,每個基因散在的突變位點數(shù)目眾多,并且同一種表型可能由不同的基因?qū)е?因而耳聾基因的基因和位點遺傳異質(zhì)性較高。由于在不同的地區(qū)和種族中耳聾基因突變譜和優(yōu)勢突變不同,新疆地處中西亞文化交匯處的中國西北邊陲,是一個以維吾爾族為主體的多民族的地區(qū),在千百年的民族遷徙和融合中,新疆地區(qū)維吾爾族耳聾基因突變譜和優(yōu)勢突變可能有其特點。本研究對新疆維吾爾族和漢族非綜合征性耳聾人群常見耳聾基因突變位點進行檢測,以揭示維吾爾族耳聾人群常見耳聾基因突變的特點及與漢族的區(qū)別。 方法：選取新疆地區(qū)具有代表性的維吾爾族和漢族耳聾人群集中學(xué)校、醫(yī)院和社會救助機構(gòu)作為篩查對象,包括喀什市特教學(xué)校、喀什市殘疾人聯(lián)合會、喀什市語訓(xùn)學(xué)校、昌吉市特教學(xué)校、新疆維吾爾自治區(qū)殘疾人聯(lián)合會、烏魯木齊語訓(xùn)學(xué)校和新疆醫(yī)科大學(xué)第一附屬醫(yī)院耳鼻喉科門診耳聾的患者作為非綜合征性耳聾篩查對象。采集耳聾研究對象的基本資料,行聽力學(xué)檢查和全身體查,篩選出符合非綜合征性聾的患者,同時選取新疆地區(qū)聽力正常人群維吾爾族103人和漢族70人作為對照。 抽取研究對象前臂靜脈血樣3-5ml,提取全血DNA,利用北京博奧生物有限公司設(shè)計開發(fā)的晶芯?九項遺傳性耳聾基因檢測芯片對所選樣本進行耳聾基因突變檢測,該芯片能檢測GJB2、SLC26A4、mtDNA 12s rRNA和GJB3四個基因的九個位點35delG、176del16、235delC、299～300delAT、538CT、1555AG、1494CT、2168AG和IVS7-2AG的突變。對于檢測過程中發(fā)現(xiàn)的突變位點探針信號缺失的樣本。在美國ABI 3730測序儀進一步進行基因測序研究,以明確可能存在的新的突變。 結(jié)果：在441例耳聾患者中篩選出無血緣關(guān)系的漢族和維吾爾族非綜合征型聾患者共350例,其中維吾爾族199例,漢族151例。聽力表現(xiàn)為雙側(cè)中重度以上感音神經(jīng)性耳聾。篩選出的350人中,33人有明確家族史,即同胞兄弟姐妹、父母中還存在一個或一個以上耳聾患者。其中維吾爾族耳聾患者中有22人,漢族耳聾患者中有11人。 對研究對象和對照組共523人進行突變基因檢測,發(fā)現(xiàn)四例樣本突變位點探針信號缺失,對四例樣本進行基因測序。維吾爾族和漢族研究組常見耳聾基因的突變檢出率分別為13.06%和32.45%,差異有統(tǒng)計學(xué)意義；GJB2基因在維吾爾族和漢族耳聾患者突變檢出率分別為9.05%、16.56%,差異無統(tǒng)計學(xué)意義,235delC為兩個民族耳聾患者的熱點突變,35delG為維吾爾族耳聾患者的熱點突變,187delG在維吾爾族耳聾患者中首次發(fā)現(xiàn),也是新發(fā)現(xiàn)的GJB2基因的病理性突變；SLC26A4在維吾爾族和漢族耳聾患者中的突變檢出率分別為2.01%、14.57%,差別有統(tǒng)計學(xué)意義,維吾爾族耳聾患者中的突變檢出率明顯低于漢族；mtDNA 12srRNA基因在維吾爾族和漢族耳聾患者中的突變檢出率分別為2.01%、2.65%,差異無統(tǒng)計學(xué)意義；GJB3基因在兩個民族耳聾患者中的突變檢出率低。維吾爾族研究組有明確耳聾家族史的22人中,檢測出突變3例,耳聾家族史人群檢出的陽性率為13.64%(3/22)；漢族研究組有明確耳聾家族史11人中,檢測出突變6例,耳聾家族史人群檢出的陽性率為54.55%(6/11),兩個民族中有耳聾家族史患者常見耳聾基因的陽性檢出率經(jīng)矯正卡方檢驗比較,差別有統(tǒng)計學(xué)意義,漢族研究組高于維吾爾族研究組。 結(jié)論：本研究篩查對象為維吾爾族和漢族非綜合征性聾耳聾人群,來源于喀什市特教學(xué)校、喀什市殘疾人聯(lián)合會、喀什市語訓(xùn)學(xué)校、昌吉市特教學(xué)校、新疆維吾爾自治區(qū)殘疾人聯(lián)合會、烏魯木齊語訓(xùn)學(xué)校和新疆醫(yī)科大學(xué)第一附屬醫(yī)院耳鼻喉科門診就診的患者,研究對象中既包括以維吾爾族聚居為主體的喀什、和田地區(qū)的患者,也包括了烏魯木齊及周邊地區(qū)漢族人口主要聚居地的患者,所以研究對象來源于兩個民族的主體成分。 維吾爾族研究組和對照組、漢族研究組和對照組常見耳聾基因突變檢出率分別為13.06%、1.94%、32.45%和4.28%,維吾爾族研究組和漢族研究組常見耳聾基因突變檢出率與各自對照組比較差別有統(tǒng)計學(xué)意義,研究組明顯高于對照組,表明對耳聾人群進行常見耳聾基因檢測對耳聾病因的診斷有積極的意義。維吾爾族研究組突變檢出率明顯低于漢族研究組,差別有統(tǒng)計學(xué)意義,表明維吾爾族研究組常見耳聾基因突變譜與漢族研究組不完全一樣。GJB2基因在兩個民族非綜合征性耳聾人群中仍是耳聾相關(guān)基因的主要基因,但熱點突變不盡相同。SLC26A4基因在維吾爾族研究組中的突變檢出率明顯低于漢族研究組,推測維吾爾族耳聾人群SLC26A4基因熱點突變可能與蒙古人種不同,是否存在與高加索人種熱點突變一致的位點還需要做進一步的研究來證實。所以說兩個民族耳聾患者的耳聾基因突變譜并不完全相同。因此有必要對維吾爾族耳聾患者做進一步的基因序列分析和家系研究,來豐富維吾爾族耳聾基因的突變譜并確定優(yōu)勢突變。 對耳聾基因常見突變檢測不是研究的目的,通過耳聾基因診斷的結(jié)果,對耳聾患者及家屬提供耳聾遺傳咨詢,就有關(guān)耳聾遺傳的病因、遺傳方式、診斷、防治和預(yù)后等相關(guān)問題進行溝通,對患者或其親屬生育子女時再患耳聾的風(fēng)險進行評估,并提出建議和指導(dǎo),然后結(jié)合客觀、準確的生育指導(dǎo)和干預(yù)措施,將有助于從根本上預(yù)防和阻斷遺傳耳聾患兒的出生,從而達到提高我國人口的整體素質(zhì)的目的。所以耳聾遺傳咨詢在耳聾的整體防治中具有重要的意義。
[Abstract]:Objective: 50% childhood deafness is considered to be associated with genetic factors. Up to now, 62 genes associated with non syndromic deafness have been identified. Among the numerous deafness genes found, the number of mutations per gene is numerous, and the same phenotype may be caused by different genes, thus the genes and loci of the deafness genes are found. The genetic heterogeneity is high. Due to the different mutation spectrum and dominant mutation of the deafness gene in different regions and races, Xinjiang is located in the northwest border of China and Western Asia. It is a multi-ethnic area with Uygur nationality as the main body. The mutation spectrum of the deafness gene of the Uygur in the Xinjiang area in thousands of years of ethnic migration and fusion. The characteristics of the mutation of the common deafness gene in the Uygur and Han non syndromic deafness people in Xinjiang were detected in this study to reveal the characteristics of the common deafness gene mutation in the Uygur deaf people and the difference from the Han people.
Methods: to select the representative Uygur and Han deaf people in Xinjiang to concentrate schools, hospitals and social assistance institutions as screening targets, including Kashi special education schools, Kashi disabled persons' Federation, Kashi language training school, Changji special education school, the Xinjiang Uygur Autonomous Region disabled people's Federation, Urumqi language training. In the Department of ENT, the First Affiliated Hospital of the First Affiliated Hospital of Xinjiang Medical University, the patients with deafness were screened as non syndromic deafness screening subjects. The basic data of the research subjects of deafness were collected, audiology and body examination were used to screen out patients with non syndromic deafness. At the same time, 103 Uygur people were selected from the normal hearing population in Xinjiang. 70 Han people as the control.
To extract 3-5ml from the forearm vein blood samples and extract DNA from the whole blood, nine genetic deafness gene detection chips were designed and developed by Beijing boo biological Co., Ltd. to detect the deafness gene mutation of the selected samples. The chip can detect the nine loci of GJB2, SLC26A4, mtDNA 12S rRNA and GJB3, 176del16235, 35delG, 176del16235. Mutations in delC, 299 to 300delAT, 538CT, 1555AG, 1494CT, 2168AG and IVS7-2AG. A sample of the deletion of the probe signal of the mutation site detected during detection. Further gene sequencing was carried out in the US ABI 3730 sequencer to identify possible new mutations.
Results: among the 441 Cases of deafness, 350 cases of Han and Uygur non syndromic deafness were screened out, of which 199 were Uygur and 151 in Han nationality. Hearing performance was bilateral moderate to severe sensorineural deafness. Among the 350 people, 33 had a clear family history, siblings and siblings, and parents still existed. One or more deafness patients, of whom 22 were Uygur deafness patients and 11 were Han deafness patients.
A total of 523 people in the study group and the control group were detected by mutation gene detection, and four sample mutation sites were found to be missing and four samples were sequenced. The mutation detection rates of the common deafness genes in the Uygur and Han study groups were 13.06% and 32.45%, respectively. The GJB2 gene was in Uygur and Han ears. The mutation detection rate of the deafness patients was 9.05%, 16.56%, the difference was not statistically significant. 235delC was the hot spot mutation of the deaf patients in two ethnic groups. 35delG was the hot mutation of the Uygur deafness. The 187delG was found in the Uygur deafness for the first time, and the pathological mutation of the newly discovered GJB2 gene; SLC26A4 in Uygur and Han people. The mutation detection rate in the deafness patients was 2.01% and 14.57% respectively. The mutation detection rate in the Uygur deafness was significantly lower than that of the Han nationality; the mutation detection rate of mtDNA 12srRNA gene in the Uygur and Han deafness patients was 2.01% and 2.65%, respectively, and the GJB3 gene was in two ethnic groups. The mutation detection rate in the deafness patients was low. In the Uygur study group, 3 of the 22 people with a clear family history of deafness were detected. The positive rate of the deaf family history was 13.64% (3/22); 6 cases were detected in the Han study group with a clear family history of deafness, and the positive rate was 54.55% (6/11), two in the family history of hearing loss (6/11), two The positive rate of the common deafness gene in the people with the history of deafness was compared with the corrected chi square test, the difference was statistically significant, and the Han study group was higher than the Uygur research group.
Conclusion: the objective of this study was the non syndromic deafness deafness people of Uygur and Han people, from Kashi special education school, Kashi disabled people's Federation, Kashi language training school, Changji special education school, the Xinjiang Uygur Autonomous Region Disabled Association, Urumqi language training school and the First Affiliated Hospital of Xinjiang Medical University. The patients in the outpatient department of the nasolaryngology included both the Kashi, the Uygur population and the patients in the Hotan area, and the patients in the main habitation of the Han population in Urumqi and the surrounding areas, so the subjects were derived from the main components of the two ethnic groups.
The common deafness gene mutations in the Uygur research group and the control group were 13.06%, 1.94%, 32.45% and 4.28%, respectively. The common deafness gene mutation rate in the Uygur research group and the Han study group was statistically significant compared with the control group, and the study group was obviously higher than the control group, indicating deafness in the study group. The common deafness gene detection in the population has positive significance for the diagnosis of the cause of deafness. The mutation detection rate of the Uygur study group is obviously lower than that of the Han study group, and the difference is statistically significant. It shows that the common deafness gene mutation spectrum of the Uygur study group is not exactly the same as the Han study group, and the.GJB2 gene is in the two ethnic non syndromic ears. The deaf population is still the main gene of deafness related genes, but the mutation detection rate of the.SLC26A4 gene in the Uygur study group is obviously lower than that of the Han study group. It is speculated that the SLC26A4 gene mutation of the Uygur deaf people may be different from the Mongolian species, and is the same as the hot spot mutation in the Caucasus. It is necessary to make further genetic sequence analysis and family studies in Uygur deafness to enrich the mutation spectrum of the Uygur deafness gene and determine the dominant mutation, so the mutation spectrum of the deafness of the two ethnic deafness patients is not exactly the same.
The detection of the common mutation of the deafness gene is not the purpose of the study. Through the results of the deafness gene diagnosis, the deafness patients and their families are provided with the genetic counseling on the deafness, the related problems related to the hereditary cause, the heredity, the diagnosis, the prevention and the prognosis of the deafness are communicated, and the risk of the deafness of the patients and their relatives when they have children is evaluated. It is important to estimate, put forward suggestions and guidance, and then combine objective and accurate reproductive guidance and intervention measures, which will help to prevent and block the birth of the children with hereditary deafness, so as to improve the overall quality of the population in our country. Therefore, the genetic counseling of deafness is of great significance in the overall prevention and treatment of deafness.

【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R764.43

【引證文獻】

相關(guān)期刊論文 前1條

1 王喜文;林海波;曾小情;;我國人群GJB2基因235delC突變與非綜合征性耳聾相關(guān)性的meta分析[J];中國醫(yī)藥科學(xué);2013年15期

相關(guān)碩士學(xué)位論文 前1條

1 胡暢;基于iMLDR技術(shù)的耳聾基因突變熱點的新型快速檢測方法研究[D];中南大學(xué);2013年

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本文編號：1861415