發(fā)布時(shí)間：2018-03-18 21:25

  本文選題：基因突變　切入點(diǎn)：ABCA3基因　出處：《廣西醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:研究ATP連接盒轉(zhuǎn)運(yùn)子A3(ABCA3)基因突變與新生兒呼吸窘迫綜合征(RDS)發(fā)病的關(guān)系,為防治新生兒呼吸窘迫綜合征提供基因研究資料。方法:采用病例-對照研究,共納入廣西地區(qū)胎齡大于32周的早產(chǎn)兒300例,其中RDS患兒150例(病例組),非RDS患兒150例(對照組)。抽取各研究對象外周靜脈血2ml,應(yīng)用DNA提取試劑盒提取基因組DNA,以每5個(gè)DNA建立DNA-pool。采用目標(biāo)區(qū)域捕獲技術(shù),以ABCA3為目標(biāo)基因,通過Agilent液相捕獲平臺富集目標(biāo)區(qū)域序列,應(yīng)用Illumina Hiseq2000高通量第二代測序平臺對ABCA3基因外顯子進(jìn)行深度重測序并進(jìn)行數(shù)據(jù)分析,對錯(cuò)義突變位點(diǎn)用SIFT和Polyphen2軟件進(jìn)行功能預(yù)測,確定功能性突變,通過Sanger測序?qū)δ苄酝蛔冞M(jìn)行基因型驗(yàn)證。應(yīng)用collapsing統(tǒng)計(jì)方法計(jì)算總突變的最小等位基因頻率(Minor Allele Frequency,MAF)。結(jié)果:(1)兩組共發(fā)現(xiàn)變異位點(diǎn)307種,其中錯(cuò)義變異10種,同義變異15種,內(nèi)含子變異258種,剪接區(qū)域變異2種,上游基因變異位點(diǎn)2種,下游基因變異位點(diǎn)13種,3’端非編碼區(qū)3種,5’端非編碼區(qū)4種。(2)病例組未發(fā)現(xiàn)突變。對照組發(fā)現(xiàn)2種突變:位于Exon 10 c.1009 GA p.V337M和位于Exon 27 c.4149 CG p.I1383M,均為雜合突變。應(yīng)用Collapsing方法合并突變進(jìn)行統(tǒng)計(jì):ABCA3基因基因突變在對照組人群的MAF均為0.67%,攜帶率均為1.33%。結(jié)論:ABCA3基因在中國廣西地區(qū)早產(chǎn)兒人群中突變頻率極低,尚無足夠依據(jù)認(rèn)為ABCA3基因突變是早產(chǎn)兒RDS發(fā)病的高危因素。
[Abstract]:Objective: to study the relationship between the mutation of ATP cassette transporter A3 / ABCA3 gene and the pathogenesis of neonatal respiratory distress syndrome (RDS), and to provide genetic data for the prevention and treatment of neonatal respiratory distress syndrome (RDS). Methods: a case-control study was used to study the relationship between the mutation of ABCA3 gene and the pathogenesis of neonatal respiratory distress syndrome. A total of 300 premature infants with gestational age longer than 32 weeks were included in Guangxi. Among them, 150 cases of RDS (case group) and 150 cases of non RDS (control group) were collected from peripheral venous blood of each study object. Genomic DNAs were extracted by DNA extraction kit, and DNA-pools were established for every 5 DNA. Using target region capture technique, ABCA3 was used as target gene. The target region sequence was enriched by Agilent liquid phase capture platform. The exon of ABCA3 gene was deeply resequenced and analyzed by Illumina Hiseq2000 high-throughput second-generation sequencing platform. The missense mutation sites were predicted by SIFT and Polyphen2 software. Functional mutations were identified, and genotypes of functional mutations were verified by Sanger sequencing. The minimum allelic frequency of total mutations was calculated by collapsing method. The results showed that there were 307 mutation sites in the two groups, of which 10 were missense mutations. There were 15 synonymous mutations, 258 intron variations, 2 splicing region variations, and 2 upstream gene mutation sites. No mutation was found in 13 species of gene mutation loci at the 3'terminal region and 4 species in the 5'terminal noncoding region. In the control group, two mutations were found: Exon 10 c. 1009, GA p.V337M, and Exon 27 c. 4149 CG p.I1383M. all of them were heterozygous mutations. The MAF of the Collapsing gene mutation was 0.67 in the control group, and the carrying rate was 1.33. Conclusion the mutation frequency of the 10% ABCA3 gene is very low in the preterm infants in Guangxi, China. There is no sufficient evidence that ABCA3 gene mutation is a high risk factor for preterm infants with RDS.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R722.1

【相似文獻(xiàn)】

相關(guān)會議論文 前2條

1 王亞洲;陳玉君;;ABCA3基因變異與新生兒呼吸窘迫綜合征的相關(guān)性研究[A];中華醫(yī)學(xué)會第十七次全國兒科學(xué)術(shù)大會論文匯編（上冊）[C];2012年

2 江林;杜立中;;ABCA3基因多態(tài)性與早產(chǎn)兒RDS發(fā)病相關(guān)性的臨床研究[A];第六屆江浙滬兒科學(xué)術(shù)會議暨兒科學(xué)基礎(chǔ)與臨床研究進(jìn)展學(xué)術(shù)班論文匯編[C];2009年

相關(guān)碩士學(xué)位論文 前2條

1 寧辛未;ABCA3基因突變與新生兒呼吸窘迫綜合征發(fā)病的研究[D];廣西醫(yī)科大學(xué);2017年

2 田文軍;ABCA3基因多態(tài)性與早產(chǎn)兒呼吸窘迫綜合征的相關(guān)性研究[D];廣西醫(yī)科大學(xué);2015年

，

本文編號：1631368