GABRB3基因启动子区rs4906902和rs8179184位点遗传多态性与精神分裂症的相关性及法医学意义
发布时间：2018-09-01 08:44
【摘要】： 前言 γ-氨基丁酸(Gamma-aminobutyric acid,GABA)A型受体β_3亚基基因(GABRB3)具有遗传多态性,并通过影响或改变中枢神经系统其它神经递质的作用而与人类精神疾病密切相关。因此,β_3亚基基因可能成为法医学个人识别与亲权鉴定新的遗传标记及司法精神病鉴定的参考遗传学指标。 人类GABRB3基因位于15q11.2-q12,第1a外显子启动子区有多个SNP位点。目前国内尚无对这些位点遗传多态性与精神分裂症相关性的报道;虽然国外学者在相关领域已经取得了一定的研究成果,但由于不同种族和不同民族间的差异,使国外的研究成果不能直接应用于中国人群。本研究应用DNA测序的方法,调查GABRB3基因启动子区SNP位点多态性在汉族人群和精神分裂症患者中的频率分布,分析它们的遗传多态性在正常人群的分布情况,与精神分裂症之间的关联性,为人们的精神生理功能的估计提供新的遗传学指标,并为法医学应用提供基础数据。 材料和方法 采集210例(男性102例,女性108例)中国北方汉族健康人血样和206例汉族精神分裂症患者血液样品(其中男性104例,女性102例),共计416例,其中精神分裂症病人诊断同时符合中国精神障碍分类与诊断标准第三版和美国精神障碍诊断与统计手册第四版。 应用PCR技术扩增GABRB3基因启动子区,包含rs4906902和rs8179184多态性位点的片段,通过DNA测序法进行基因分型。 实验结果 在210例中国北方汉族群体中,GABRB3基因启动区rs4906902和rs8179184位点紧密连锁,共检出三种基因型和两种单倍型:纯合型TT-GG为107例,频率为0.5095;杂合型TC-GA为85例,频率为0.4048;纯合型CC-AA为18例,频率为0.0857。单倍型T-G频率为0.7119,单倍型C-A频率为0.2281。基因型分布完全符合Hardy-Weinberg平衡定律。 在206例精神分裂症患者中,TT-GG为71例,频率为0.3447;TC-GA为98例,频率为0.4757;CC-AA为37例,频率为0.1796。单倍型T-G频率为0.5825,单倍型C-A频率为0.4175。基因型分布完全符合Hardy-Weinberg平衡定律。 精神分裂症与对照组之间比较,单倍型频率分布差异在各组之间P＜0.05。而将各人群按性别分组,精神分裂症按临床亚型分组再作比较可见:精神分裂症组女性、偏执型精神分裂症组女性、未定型精神分裂症组女性与对照组女性单倍型频率分布相比较,P＜0.05;母系家族史精神分裂症患者组与对照组单倍型频率分布相比较,P＜0.05。 讨论 根据GABRB3基因启动子部位rs4906902和rs8179184多态性位点在中国北方汉族中,单倍型频率和基因型频率分别计算得出:该单倍型位点的DP值为0.566,H值为0.411,PE值为0.163,PIC值为0.388。该位点属于具有中等鉴别能力的遗传标记系统,在法医个人识别和亲子鉴定中具有较高的应用价值。 本研究调查了GABRB3基因启动子区单倍型在中国北方汉族,精神分裂症群体中的频率分布,经过统计学χ~2分析,结果表明单倍型C-A在精神分裂症患者中分布明显高于对照组,单倍型C-A可能与精神分裂症相关。女性精神分裂症患者的单倍型C-A频率明显高于男性患者;母系家族史患者单倍型C-A频率远远高于父系家族史患者。 结论 γ-氨基丁酸A型受体β3亚基基因启动子区单倍型,在中国北方汉族群体中具有较好的遗传多态性,适合作为法医学个人识别和亲子鉴定应用的遗传标记。C-A单倍型可能与精神分裂症有相关性。
[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.
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：D919.4;R749.3
本文编号：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.
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：D919.4;R749.3
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