GABRB3基因啟動子區(qū)rs4906902和rs8179184位點(diǎn)遺傳多態(tài)性與精神分裂癥的相關(guān)性及法醫(yī)學(xué)意義
發(fā)布時(shí)間：2018-09-01 08:44
【摘要】： 前言 γ-氨基丁酸(Gamma-aminobutyric acid,GABA)A型受體β_3亞基基因(GABRB3)具有遺傳多態(tài)性,并通過影響或改變中樞神經(jīng)系統(tǒng)其它神經(jīng)遞質(zhì)的作用而與人類精神疾病密切相關(guān)。因此,β_3亞基基因可能成為法醫(yī)學(xué)個(gè)人識別與親權(quán)鑒定新的遺傳標(biāo)記及司法精神病鑒定的參考遺傳學(xué)指標(biāo)。 人類GABRB3基因位于15q11.2-q12,第1a外顯子啟動子區(qū)有多個(gè)SNP位點(diǎn)。目前國內(nèi)尚無對這些位點(diǎn)遺傳多態(tài)性與精神分裂癥相關(guān)性的報(bào)道;雖然國外學(xué)者在相關(guān)領(lǐng)域已經(jīng)取得了一定的研究成果,但由于不同種族和不同民族間的差異,使國外的研究成果不能直接應(yīng)用于中國人群。本研究應(yīng)用DNA測序的方法,調(diào)查GABRB3基因啟動子區(qū)SNP位點(diǎn)多態(tài)性在漢族人群和精神分裂癥患者中的頻率分布,分析它們的遺傳多態(tài)性在正常人群的分布情況,與精神分裂癥之間的關(guān)聯(lián)性,為人們的精神生理功能的估計(jì)提供新的遺傳學(xué)指標(biāo),并為法醫(yī)學(xué)應(yīng)用提供基礎(chǔ)數(shù)據(jù)。 材料和方法 采集210例(男性102例,女性108例)中國北方漢族健康人血樣和206例漢族精神分裂癥患者血液樣品(其中男性104例,女性102例),共計(jì)416例,其中精神分裂癥病人診斷同時(shí)符合中國精神障礙分類與診斷標(biāo)準(zhǔn)第三版和美國精神障礙診斷與統(tǒng)計(jì)手冊第四版。 應(yīng)用PCR技術(shù)擴(kuò)增GABRB3基因啟動子區(qū),包含rs4906902和rs8179184多態(tài)性位點(diǎn)的片段,通過DNA測序法進(jìn)行基因分型。 實(shí)驗(yàn)結(jié)果 在210例中國北方漢族群體中,GABRB3基因啟動區(qū)rs4906902和rs8179184位點(diǎn)緊密連鎖,共檢出三種基因型和兩種單倍型:純合型TT-GG為107例,頻率為0.5095;雜合型TC-GA為85例,頻率為0.4048;純合型CC-AA為18例,頻率為0.0857。單倍型T-G頻率為0.7119,單倍型C-A頻率為0.2281�；蛐头植纪耆螲ardy-Weinberg平衡定律。 在206例精神分裂癥患者中,TT-GG為71例,頻率為0.3447;TC-GA為98例,頻率為0.4757;CC-AA為37例,頻率為0.1796。單倍型T-G頻率為0.5825,單倍型C-A頻率為0.4175�；蛐头植纪耆螲ardy-Weinberg平衡定律。 精神分裂癥與對照組之間比較,單倍型頻率分布差異在各組之間P＜0.05。而將各人群按性別分組,精神分裂癥按臨床亞型分組再作比較可見:精神分裂癥組女性、偏執(zhí)型精神分裂癥組女性、未定型精神分裂癥組女性與對照組女性單倍型頻率分布相比較,P＜0.05;母系家族史精神分裂癥患者組與對照組單倍型頻率分布相比較,P＜0.05。 討論 根據(jù)GABRB3基因啟動子部位rs4906902和rs8179184多態(tài)性位點(diǎn)在中國北方漢族中,單倍型頻率和基因型頻率分別計(jì)算得出:該單倍型位點(diǎn)的DP值為0.566,H值為0.411,PE值為0.163,PIC值為0.388。該位點(diǎn)屬于具有中等鑒別能力的遺傳標(biāo)記系統(tǒng),在法醫(yī)個(gè)人識別和親子鑒定中具有較高的應(yīng)用價(jià)值。 本研究調(diào)查了GABRB3基因啟動子區(qū)單倍型在中國北方漢族,精神分裂癥群體中的頻率分布,經(jīng)過統(tǒng)計(jì)學(xué)χ~2分析,結(jié)果表明單倍型C-A在精神分裂癥患者中分布明顯高于對照組,單倍型C-A可能與精神分裂癥相關(guān)。女性精神分裂癥患者的單倍型C-A頻率明顯高于男性患者;母系家族史患者單倍型C-A頻率遠(yuǎn)遠(yuǎn)高于父系家族史患者。 結(jié)論 γ-氨基丁酸A型受體β3亞基基因啟動子區(qū)單倍型,在中國北方漢族群體中具有較好的遺傳多態(tài)性,適合作為法醫(yī)學(xué)個(gè)人識別和親子鑒定應(yīng)用的遺傳標(biāo)記。C-A單倍型可能與精神分裂癥有相關(guān)性。
[Abstract]:Preface
Gamma-aminobutyric acid (GABA) receptor beta_3 subunit gene (GABRB3) has genetic polymorphism and is closely related to human psychiatric disorders by affecting or altering other neurotransmitters in the central nervous system. Therefore, the beta_3 subunit gene may become a new genetic marker for forensic personal identification and paternity testing. Reference genetic indicators for forensic psychiatric expertise.
The human GABRB3 gene is located at 15q11.2-q12, and there are several SNP loci in the promoter region of exon 1a. At present, there are no reports about the relationship between genetic polymorphism of these loci and schizophrenia in China; although foreign scholars have made certain research results in related fields, but due to the differences between different races and different nationalities, foreign scholars have made some progress. The results of this study can not be directly applied to the Chinese population. DNA sequencing was used to investigate the frequency distribution of SNP polymorphisms in the promoter region of GABRB3 gene in the Han population and schizophrenic patients, and to analyze the distribution of genetic polymorphisms in the normal population and the association between genetic polymorphisms and schizophrenia. The estimation of the physiological function of God provides new genetic indicators and provides basic data for forensic application.
Materials and methods
A total of 416 schizophrenic patients (104 males and 102 females) were collected from 210 healthy subjects (102 males and 108 females) and 206 schizophrenic patients (102 females). The diagnosis of schizophrenic patients accorded with the Chinese Classification and Diagnostic Standards for Mental Disorders (3rd edition) and the American Diagnostic and Statistical Hands for Mental Disorders (ASD). Volume fourth edition.
The promoter region of GABRB3 gene was amplified by polymerase chain reaction (PCR) including rs4906902 and rs8179184 polymorphisms, and genotyped by DNA sequencing.
experimental result
Three genotypes and two haplotypes were detected in 210 northern Chinese Han population: homozygous TT-GG in 107 cases, with a frequency of 0.5095; heterozygous TC-GA in 85 cases, with a frequency of 0.4048; homozygous CC-AA in 18 cases, with a frequency of 0.0857. The frequency distribution of 0.2281. genotype accords with the Hardy-Weinberg equilibrium law.
Among 206 schizophrenic patients, TT-GG was 71, with a frequency of 0.3447, TC-GA was 98, with a frequency of 0.4757, CC-AA was 37, with a frequency of 0.1796. The T-G frequency of haplotype was 0.5825, and the C-A frequency of haplotype was 0.4175.
The difference of haplotype frequency distribution between schizophrenia group and control group was P The haplotype frequencies of schizophrenic patients with maternal family history were higher than those of control group (P < 0.05).
discuss
The haplotype frequencies and genotype frequencies of rs4906902 and rs8179184 polymorphic loci in the promoter region of GABRB3 gene were calculated in the Han population of northern China. The results showed that the haplotype had a DP value of 0.566, a H value of 0.411, a PE value of 0.163, and a PIC value of 0.388. The haplotype belonged to a genetic marker system with moderate discriminant ability and belonged to a forensic individual. Recognition and paternity testing are of high application value.
This study investigated the frequency distribution of haplotypes of the promoter region of GABRB3 gene in Chinese northern Han population with schizophrenia. Statistical_~2 analysis showed that the distribution of haplotype C-A in schizophrenic patients was significantly higher than that in the control group, and haplotype C-A might be associated with schizophrenia. The frequency of haplotype C-A in patients with maternal family history was much higher than that in patients with paternal family history.
conclusion
The promoter haplotype of gamma-aminobutyric acid type A receptor beta 3 subunit gene has good genetic polymorphism in northern Chinese Han population and is suitable for forensic personal identification and paternity testing. C-A haplotype may be associated with schizophrenia.
【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：D919.4;R749.3
本文編號：2216674
[Abstract]:Preface
Gamma-aminobutyric acid (GABA) receptor beta_3 subunit gene (GABRB3) has genetic polymorphism and is closely related to human psychiatric disorders by affecting or altering other neurotransmitters in the central nervous system. Therefore, the beta_3 subunit gene may become a new genetic marker for forensic personal identification and paternity testing. Reference genetic indicators for forensic psychiatric expertise.
The human GABRB3 gene is located at 15q11.2-q12, and there are several SNP loci in the promoter region of exon 1a. At present, there are no reports about the relationship between genetic polymorphism of these loci and schizophrenia in China; although foreign scholars have made certain research results in related fields, but due to the differences between different races and different nationalities, foreign scholars have made some progress. The results of this study can not be directly applied to the Chinese population. DNA sequencing was used to investigate the frequency distribution of SNP polymorphisms in the promoter region of GABRB3 gene in the Han population and schizophrenic patients, and to analyze the distribution of genetic polymorphisms in the normal population and the association between genetic polymorphisms and schizophrenia. The estimation of the physiological function of God provides new genetic indicators and provides basic data for forensic application.
Materials and methods
A total of 416 schizophrenic patients (104 males and 102 females) were collected from 210 healthy subjects (102 males and 108 females) and 206 schizophrenic patients (102 females). The diagnosis of schizophrenic patients accorded with the Chinese Classification and Diagnostic Standards for Mental Disorders (3rd edition) and the American Diagnostic and Statistical Hands for Mental Disorders (ASD). Volume fourth edition.
The promoter region of GABRB3 gene was amplified by polymerase chain reaction (PCR) including rs4906902 and rs8179184 polymorphisms, and genotyped by DNA sequencing.
experimental result
Three genotypes and two haplotypes were detected in 210 northern Chinese Han population: homozygous TT-GG in 107 cases, with a frequency of 0.5095; heterozygous TC-GA in 85 cases, with a frequency of 0.4048; homozygous CC-AA in 18 cases, with a frequency of 0.0857. The frequency distribution of 0.2281. genotype accords with the Hardy-Weinberg equilibrium law.
Among 206 schizophrenic patients, TT-GG was 71, with a frequency of 0.3447, TC-GA was 98, with a frequency of 0.4757, CC-AA was 37, with a frequency of 0.1796. The T-G frequency of haplotype was 0.5825, and the C-A frequency of haplotype was 0.4175.
The difference of haplotype frequency distribution between schizophrenia group and control group was P The haplotype frequencies of schizophrenic patients with maternal family history were higher than those of control group (P < 0.05).
discuss
The haplotype frequencies and genotype frequencies of rs4906902 and rs8179184 polymorphic loci in the promoter region of GABRB3 gene were calculated in the Han population of northern China. The results showed that the haplotype had a DP value of 0.566, a H value of 0.411, a PE value of 0.163, and a PIC value of 0.388. The haplotype belonged to a genetic marker system with moderate discriminant ability and belonged to a forensic individual. Recognition and paternity testing are of high application value.
This study investigated the frequency distribution of haplotypes of the promoter region of GABRB3 gene in Chinese northern Han population with schizophrenia. Statistical_~2 analysis showed that the distribution of haplotype C-A in schizophrenic patients was significantly higher than that in the control group, and haplotype C-A might be associated with schizophrenia. The frequency of haplotype C-A in patients with maternal family history was much higher than that in patients with paternal family history.
conclusion
The promoter haplotype of gamma-aminobutyric acid type A receptor beta 3 subunit gene has good genetic polymorphism in northern Chinese Han population and is suitable for forensic personal identification and paternity testing. C-A haplotype may be associated with schizophrenia.
【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：D919.4;R749.3
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