PLXNB3基因多态性与人类认知能力的关系研究
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摘要
认知能力是人们生活中最为重要的能力之一,也是人们关注的焦点,在人群中的遗传度约为50%。近年来,随着神经生物学和分子生物学的发展,利用行为遗传学、行为基因组学和影像遗传学的研究手段和方法对认知能力进行研究,尤其对认知能力与基因关系的研究已成为当前心理学和遗传学交叉研究的热点,不仅对促进正在形成的认知神经遗传学有重要的基础研究意义,而且在优生咨询、新药开发、认知障碍的分子诊断以及儿童未来的个性化教育等方面也有实际的应用前景。
目前,研究较多的主要是影响神经递质代谢、神经信号传导和神经系统发育的相关基因与人类神经、精神类疾病以及认知能力的关系。在神经系统发育过程中,神经元的轴突只有沿特定的路径延伸,精确的抵达与其建立突触联系的靶细胞的胞体、树突或轴突才能形成具有正常生理功能的神经网络。然而,参与轴突引导过程的PLXNB3基因与人类认知能力关系的研究还很少见有报道。
本研究选择西安市某高等院校本、专科各专业一年级910名新生作为研究对象,对其进行工作记忆、中央执行功能、空间认知、长时记忆、言语认知和一般流体智力等六类认知能力共15项任务的测验。在PLXNB3基因上选择rs2266879、rs6643791以及rs5987155三个功能SNP位点和rs2266885一个标记SNP位点,用PCR-SSCP和PCR-RFLP对其进行基因分型。最后用FoxPro6.0、Haploview4.0和SPSS10.0软件包完成数据的整理和统计分析。
基于一般线性模型的单因素方差分析表明,rs2266879在男性和女性人群中都与定位能力显著性相关(p=0.020和p=0.030),并提示可能还与其工作记忆和言语认知能力有关；rs5987155在男性人群中与抑制能力显著性相关(p=0.022),并提示可能还与空间认知能力有关；rs6643791和rs2266885在两种人群中均未发现其与任何一项认知功能具有相关性,但提示rs6643791位点可能与男性人群空间认知能力有关。然而,与国外研究相比,三个功能多态位点在我们的汉族人群中未发现它们与言语认知能力的相关性。
本研究结果提示,PLXNB3基因在中国汉族人群中选择性地影响其定位和抑制两种特殊认知能力。但是,这一初步结论尚需作进一步的研究和探讨。
Cognitive ability, with about 50% degree of heritability, is one of the most important abilities in people's daily life, and has come into our focus. In recent years, with the development of neurobiology and molecular biology, researches about cognitive ability, especially about the relationship between it and genes using behavioral genetics, behavior genomics and imaging genetics as the methods and tools have become one hotspot in present psychology and genetics fields, which not only is very important to promote the basic researches for emerging cognitive neurogenetics, but also has practical prospects of application for eugenic counseling, development of new medicine, molecular diagnosis of cognitive disorder, children's individualized education in the future.
At the moment, more researches are mainly about the relationship between related genes and human nervous or mental disorders and cognitive ability, and these genes mainly involve in neurotransmitter metabolism, signal transduction and nervous system development. During the development of nervous system, the generation of physiological and functional neuronal network requires the precise navigation of axons along specific pathways to their appropriate targets, such as cell bodies, dendrites or other axons. However, researches on the relationship between the involved PLXNB3 gene and human cognitive ability are still rare.
In the study, the subjects were consisting of 910 fresh undergraduate and specialized students from all majors of some a college in Xi'an. A battery of cognitive abilities including working memory, central executive function, spatial cognitive ability, long-term memory, verbal cognitive ability and general fluid intelligence was tested among them. Three functional single nucleotide polymorphisms (SNPs) (rs2266879, rs6643791 and rs5987155) and one genetic marker (rs2266885) in PLXNB3 gene were identified based on PCR-SSCP and PCR-RFLP genotyping methods. At last, the collation of data and statistical analysis were finished using FoxPro6.0, Haploview4.0 and SPSS 10.0 software package.
The one-way ANOVA analysis based on general linear model showed that rs2266879 was significantly associated with localization in both males and females and might be associated with working mermory and verbal cognitive ability. rs5987155 was significantly associated with inhibition only in males, but might be associated with spatial cognitive ability. Both rs6643791 and rs2266885 didn't show association with any cognitive abilities, but the rs6643791 might be associated with spatial cognitive ability in males. Unfortunately, three functional SNPs also did not show association with verbal cognitive ability in the healthy Han population compared with overseas research.
The results of this study indicated that PLXNB3 gene selectively influences on human cognitive ability in Chinese Han population, but further study and discussion are needed to examine the preliminary findings.
目前,研究较多的主要是影响神经递质代谢、神经信号传导和神经系统发育的相关基因与人类神经、精神类疾病以及认知能力的关系。在神经系统发育过程中,神经元的轴突只有沿特定的路径延伸,精确的抵达与其建立突触联系的靶细胞的胞体、树突或轴突才能形成具有正常生理功能的神经网络。然而,参与轴突引导过程的PLXNB3基因与人类认知能力关系的研究还很少见有报道。
本研究选择西安市某高等院校本、专科各专业一年级910名新生作为研究对象,对其进行工作记忆、中央执行功能、空间认知、长时记忆、言语认知和一般流体智力等六类认知能力共15项任务的测验。在PLXNB3基因上选择rs2266879、rs6643791以及rs5987155三个功能SNP位点和rs2266885一个标记SNP位点,用PCR-SSCP和PCR-RFLP对其进行基因分型。最后用FoxPro6.0、Haploview4.0和SPSS10.0软件包完成数据的整理和统计分析。
基于一般线性模型的单因素方差分析表明,rs2266879在男性和女性人群中都与定位能力显著性相关(p=0.020和p=0.030),并提示可能还与其工作记忆和言语认知能力有关；rs5987155在男性人群中与抑制能力显著性相关(p=0.022),并提示可能还与空间认知能力有关；rs6643791和rs2266885在两种人群中均未发现其与任何一项认知功能具有相关性,但提示rs6643791位点可能与男性人群空间认知能力有关。然而,与国外研究相比,三个功能多态位点在我们的汉族人群中未发现它们与言语认知能力的相关性。
本研究结果提示,PLXNB3基因在中国汉族人群中选择性地影响其定位和抑制两种特殊认知能力。但是,这一初步结论尚需作进一步的研究和探讨。
Cognitive ability, with about 50% degree of heritability, is one of the most important abilities in people's daily life, and has come into our focus. In recent years, with the development of neurobiology and molecular biology, researches about cognitive ability, especially about the relationship between it and genes using behavioral genetics, behavior genomics and imaging genetics as the methods and tools have become one hotspot in present psychology and genetics fields, which not only is very important to promote the basic researches for emerging cognitive neurogenetics, but also has practical prospects of application for eugenic counseling, development of new medicine, molecular diagnosis of cognitive disorder, children's individualized education in the future.
At the moment, more researches are mainly about the relationship between related genes and human nervous or mental disorders and cognitive ability, and these genes mainly involve in neurotransmitter metabolism, signal transduction and nervous system development. During the development of nervous system, the generation of physiological and functional neuronal network requires the precise navigation of axons along specific pathways to their appropriate targets, such as cell bodies, dendrites or other axons. However, researches on the relationship between the involved PLXNB3 gene and human cognitive ability are still rare.
In the study, the subjects were consisting of 910 fresh undergraduate and specialized students from all majors of some a college in Xi'an. A battery of cognitive abilities including working memory, central executive function, spatial cognitive ability, long-term memory, verbal cognitive ability and general fluid intelligence was tested among them. Three functional single nucleotide polymorphisms (SNPs) (rs2266879, rs6643791 and rs5987155) and one genetic marker (rs2266885) in PLXNB3 gene were identified based on PCR-SSCP and PCR-RFLP genotyping methods. At last, the collation of data and statistical analysis were finished using FoxPro6.0, Haploview4.0 and SPSS 10.0 software package.
The one-way ANOVA analysis based on general linear model showed that rs2266879 was significantly associated with localization in both males and females and might be associated with working mermory and verbal cognitive ability. rs5987155 was significantly associated with inhibition only in males, but might be associated with spatial cognitive ability. Both rs6643791 and rs2266885 didn't show association with any cognitive abilities, but the rs6643791 might be associated with spatial cognitive ability in males. Unfortunately, three functional SNPs also did not show association with verbal cognitive ability in the healthy Han population compared with overseas research.
The results of this study indicated that PLXNB3 gene selectively influences on human cognitive ability in Chinese Han population, but further study and discussion are needed to examine the preliminary findings.
引文
参考文献
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