本文選題：非綜合征性唇腭裂 + 病因　； 參考：《首都醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的本研究的目的是通過SNa PShot技術(shù)檢測EPHA3基因單核苷酸多態(tài)性(Single N ucleotide polymorphism,SNP),探討EPHA3基因SNPs與非綜合征性唇腭裂(non-syndromic cleft of lip with or without palate,NSCL/P)發(fā)病的關(guān)系。并通過SNPinfo和mi RNASNP在線軟件,對潛在的功能性SNPs進(jìn)行生物信息學(xué)分析,初步分析其潛在的功能學(xué)意義。方法收集180例NSCL/P患者及167例正常對照個體樣本,通過SNa PShot技術(shù)檢測EPHA3基因5個SNPs(rs7650466、rs1398197、rs17801309、rs1054750和rs7632427),采用Plink軟件包分析不同位點(diǎn)的基因型頻率是否符合遺傳平衡檢驗(yàn);并分析5個位點(diǎn)等位基因及基因型與NSCL/P發(fā)病的關(guān)系。應(yīng)用Haplo View軟件進(jìn)行連鎖不平衡分析(linkage disequilibrium,LD)及單體型分析。應(yīng)用SNPinfo和mi RN ASNP在線軟件進(jìn)行生物信息學(xué)分析。結(jié)果5個單核苷酸多態(tài)性位點(diǎn)基因型頻率分布均符合遺傳平衡檢驗(yàn)。LD及單倍型分析發(fā)現(xiàn)5個位點(diǎn)之間不存在連鎖不平衡現(xiàn)象,不構(gòu)成單倍型。rs7650466T等位基因頻率在NSCL/P(OR=0.245,95%CI=0.159-0.379,Pχ2=2.803×10-11,校正Pχ2=1.401×10-10)及CL/P(OR=0.205,95%CI=0.126-0.333,Pχ2=9.138×10-12,校正Pχ2=4.569×10-11)組間有統(tǒng)計(jì)學(xué)差異。rs7650466 T等位基因與NSCL/P(OR=0.211,95%CI=0.131-0.338,P=9.763×10-11,校正P=4.881×10-10)和CL/P(OR=0.176,95%CI=0.104-0.297,P=7.234×10-11,校正P=3.617×10-10)發(fā)病關(guān)聯(lián)程度較高,rs7650466 T等位基因有保護(hù)作用,并且在顯性模型邏輯回歸中,rs7650466 T等位基因在NSCL/P(校正P=8.18×10-10)和CL/P(校正P=3.139×10-10)中為顯性遺傳作用。而其余4個SNPs等位基因在各組均無統(tǒng)計(jì)學(xué)意義,并且這5個SNPs的基因型在各組均無統(tǒng)計(jì)學(xué)意義。在生物信息學(xué)分析中,SNPinfo在線軟件分析發(fā)現(xiàn)EPHA3基因的rs7650466為mi R-1255a、mi R-125a-3p、mi R-143和mi R-552的潛在匹配位點(diǎn),并且mi RN ASNP在線軟件分析發(fā)現(xiàn),在正常情況下EPHA3-rs7650466 C等位基因與mi R-2052種子區(qū)的G等位基因結(jié)合,當(dāng)EPHA3-rs7650466 C突變?yōu)門時,EPHA3基因3'-UTR與mi R-2052的結(jié)合力可能會降低,導(dǎo)致改變基因的表達(dá)水平。結(jié)論在中國漢族人群中,EPHA3基因rs7650466與NSCL/P發(fā)病相關(guān)聯(lián),分層分析發(fā)現(xiàn)rs7650466與CL/P發(fā)病相關(guān)聯(lián),而與ICP發(fā)病無明顯相關(guān)性。
[Abstract]:The purpose of this study was to detect the relationship between the EPHA3 gene single nucleotide polymorphisms (Single N ucleotide polymorphism, SNP) by SNa PShot technique and the relationship between the EPHA3 gene SNPs and the pathogenesis of non syndromic cleft lip and palate. Functional SNPs was analyzed by bioinformatics, and its potential functional significance was preliminarily analyzed. Methods 180 cases of NSCL/P and 167 normal controls were collected, and 5 SNPs of EPHA3 gene (rs7650466, rs1398197, rs17801309, rs1054750 and rs7632427) were detected by SNa PShot technique, and the genotype frequency of different loci was analyzed by the Plink software package. Whether the rate was consistent with the genetic balance test; and the relationship between 5 alleles and genotypes and the incidence of NSCL/P was analyzed. Haplo View software was used to carry out linkage disequilibrium analysis (linkage disequilibrium, LD) and haplotype analysis. Bioinformatics analysis was carried out with SNPinfo and MI RN ASNP online software. Results of 5 single nucleotide polymorphisms were found. The frequency distribution of point genotypes conformed to genetic balance test.LD and haplotype analysis found that there was no linkage disequilibrium between 5 loci, which did not constitute the frequency of.Rs7650466T alleles of haplotype at NSCL/P (OR=0.245,95%CI=0.159-0.379, P 2=2.803 x, P x 2=1.401 * 10-10) and CL/P (OR=0.205,95%CI=0.126-0.333, P x 2=9.138 * 1). 0-12, the correction of P x 2=4.569 x 10-11) was statistically different between.Rs7650466 T alleles and NSCL/P (OR=0.211,95%CI=0.131-0.338, P=9.763 x 10-11, correction P=4.881 x 10-10) and CL/P (OR=0.176,95%CI=0.104-0.297, P=7.234 x 10-11, correcting P=3.617 x 10-10). In the logistic regression model, rs7650466 T alleles are dominant in NSCL/P (corrected P=8.18 x 10-10) and CL/P (corrected P=3.139 x 10-10). The remaining 4 SNPs alleles are not statistically significant in each group, and the 5 SNPs genotypes have no statistical significance in each group. In bioinformatics analysis, SNPinfo online software It was found that the rs7650466 of the EPHA3 gene was the potential matching site of MI R-1255a, MI R-125a-3p, MI R-143 and MI R-552. In Chinese Han population, EPHA3 gene rs7650466 is associated with the pathogenesis of NSCL/P. Stratified analysis found that rs7650466 is associated with the pathogenesis of CL/P and has no significant correlation with the pathogenesis of ICP.
【學(xué)位授予單位】：首都醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R782.2

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本文編號：1953243