【作者】 蔺博超；

【导师】 谢小冬；

【作者基本信息】 兰州大学 ， 遗传学， 2012， 硕士

【摘要】 研究背景：在众多的人类遗传表型性状中,人类身高是一种高度遗传的经典的多基因互作的表型性状。而语言是人类特有的精神活动和高级神经活动,是一种白发学习并通过模仿得来的一种行为模式。视力则是人类最近几十年变化最显著的表型性状之一,且近视已经成为世界上发病率最高的眼病。寻找与这三种人类表型性状有关的基因一直是人类遗传学的研究热点。最近几年GWAS(genome wide association studies,全基因组关联性研究1方法的应用已经在这三个人类表型性状的基因定位取得了巨大进步：在白种人群中找到了一系列与人类身高有关的基因。FOXP2的单核苷酸多态性证明与KE家族(一种语言功能障碍症1、自闭症和精神分裂有关。RASGRF1基因的单核苷酸多态位点在高加索人群中与高度近视显著相关,然而这些基因多态性研究在中国人群中相关研究却没有报道。身高基因的多态性在人类生长发育过程中对身高指数调节机制和发挥作用,FOXP2多态性是否与中国西北不同民族的语言划分是否有关系,RASGRF1基因的多态性在中国西北人群生长发育过程中对视力指数调节机制和发挥作用尚不明确。通过对基因遗传多态性的研究,探索该基因多态性与中国西北人群三个遗传性状的关系,为研究与中国西北人群性状相关的因素提供有价值的线索。最终为研究与中国人群身高、语言和近视相关的因素提供有价值的基础数据。方法：身高检测方面：选择与身高相关基因的6个SNP位点,实验对象为534例(男性315例,女性219例)中国西北部的成年健康个体。语言检测方面：选择FOXP2语言基因上5’UTR区上一个tagSNP位点-rs9640758,实验对象为462个汉族男性样本和327个东乡族男性样本。近视检测方面：选择RASGRF1基因上一个tagSNP位点-rs16970495,实验对象为205名中国西北健康无关汉族男性个体。对上述位点采用聚合酶链式反应-限制性内切酶长度多态性检测技术(PCR-RFLP)进行基因分型,对基因型及等位基因频率进行连续数量性状的统计学分析,并对数据按照样本的民族、性别和身高进行分层统计；对基因型及等位基因频率进行病例对照研究方法即x2检验。结果：各位点的多态性分析显示：身高检测方面：CDK基因rs2282978位点的三种基因型人群的身高均值在中国西北人群中无显著性差异。BMP-2基因的rs967417位点多态性与中国西北人群身高指数的差异具有显著相关性(P<0.05)。NOG基因的rs4794665位点与中国西北人群身高指数的差异具有显著相关性(P<0.05)。DYM基因的rs8099584位点多态性与中国西北人群身高指数的差异具有显著相关性(P<0.05)。而是这三个位点所在的基因的突变都是骨骼发育不良综合征显著相关。ZBTB38基因rs36440003位点在中西北人群中的多态性分布与其人群的身高指数差异有显著关联性(P<0.05)。这些位点的多态性共同解释了中国西北人群身高变化的4.88%。ITM2A基因的rs1474563位点的多态性分布只与中国西北男性群体的身高有显著相关性(P<0.05),而在女性群体中与身高无显著相关性(P>0.05)。语言检测方面：FOXP2基因的rs964075多态性分布在汉族组中和东乡族组中分布有显著性差异(p<0.05)。近视检测方面：单因素方差分析结果显示,rs16970495位点三种基因型的平均视力无显著性差异(P>0.05)。结论：身高检测方面：上述结果表明在中国西北人群中,基因BMP-2, NOG, DYM和zbtb38的rs967417、rs4794665、rs8099584和rs36440003的遗传多态性与身高指数有不同程度的显著相关性。BMP-2基因rs967417位点的C型、DYM基因rs4794665位点的A型和NOG基因位点的A型与中国西北人群的高身材显著相关。而ITM2A基因rs1474563位点的T基因型只与中国西北男性人群的高身材显著相关。语言检测方面：研究结果表明FOXP2基因rs964075位点的多态性与中国西北人群的语言类型具有相关性。近视检测方面：本研究未发现RASGRF1基因的rs16970495位点遗传多态性和中国西北人群近视易感性之间的相关性。更多还原

【Abstract】 Background:Among so many anthropologic polygenetic trait, human height is a highly heritable, classic polygenetic trait. Identification of height-related genes is a hot spot in genetic study. Speech is a form of auditory-guided, learned vocal motor behaviour that evolved in mammals and certain species of birds. Myopia is the highest eye disease, which has increasingly prevailed a lot recent years. Recently, the application of large-scale genome-wide association (GWAS) approach has made tremendous improvement in this aspect: scientists identified a subset of polymorphisms associated with human stature variation in Caucasian; the polymorphism of FOXP2is related with KE family disease (a language disorder), and the polymorphism of RASGRF1is related with myopia. However, few reports on this issue were published in Chinese people, which is evidently differs from Caucasian in genetic background. The associations of height-related genes, FOXP2and RASGRF1polymorphisms with high stature, different languages and myopia in northwest China remain elusive. The aim of our study is to select a subset of genes identified in previous GWAS studies and test their genotypes in Chinese people from northwest China, and to determine whether the correlation between the3phenotypes and the polymorphisms of the selected genes are universal or ethnic specific.Methods:In high stature aspect, selected6genes from the result of GWAS, used PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) assay in534(315of male and219of female) healthy over adult individuals which were randomly investigated in northwest of China. In language aspect, selected a tagSNP-rs9640758of FOXP2and tested it’s genotype in462males of Han and327males of Dongxiang. In myopia aspect, selected a tagSNP-rs16970495of RASGRF1and tested it’s genotype in205males of Han in northwest of China. Genotype and allele distributions were analyzed in inheritance of quantitative character study and case-control study to determine whether the correlation between the3phenotypes and gene polymorphisms.Results: In high stature aspect, the result indicted that CDK’s rs2282978was not significant associated with individual’s height in three ethnic groups, however, BMP-2’s rs967417, NOG’s rs4794665, and DYM’s rs8099594(P<0.05) were significant correlated with individual’s height in three ethnic groups. Remarkably, these three SNPs are also implicated in skeletal dysplasia syndromes. Besides, ZBTB38’s rs36440003was also significant correlated with individual’s height in three ethnic groups. Together, these SNPs accounted for approximately4.88%of the height variation in Chinese people from northwest China.ITM2A’s rs1474563was significant correlated with individual’s height in male group.In language aspect, A/A、A/G and G/G for rs964075were significantly different between Han and Dongxiang (p<0.05).In myopia aspect, the result of ANOVA test shows that RASGRF1’s rs16970495has little related with the myopia in the Northwest of Chinese population(P>0.05).Conclusion:In high stature aspect: Our data strongly suggested that the three SNPs identified in the present work may generally associate with the height trait in Chinese population. C type for rs967417, G type for rs4794665and G type for rs8099594were associated with high stature in Chinese northwest population.In language aspect, these findings suggested genetic polymorphisms of rs964075identified in our study may affect language variations in northwest of Chinese population.In myopia aspect, rs16970495of the RASGRF1gene had no significant effect on the myopia in the Northwest of Chinese population.更多还原