全反式视黄醇脱氢酶基因单核苷酸多态性连锁不平衡图谱的建立  

Establishing the linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDHS)gene

作　　者：韩伟[1] 沈晔[1] 王竞[1] Sheaping Yip Maurice K.H.Yap 

机构地区：[1]浙江大学医学院附属第一医院眼科中心,杭州310003 [2]香港理工大学眼视光学院

出　　处：《中华眼科杂志》2006年第7期642-648,共7页Chinese Journal of Ophthalmology

摘　　要：目的建立全反式视黄醇脱氢酶基因单核苷酸多态性连锁不平衡图谱。方法采用变性高效液相色谱分析技术(DHPLC),在4个汉族人DNA样品池(每个由5个样本组成)中筛查SNP,并在150个汉族人样本中测定基因频率。采用Haploview和EH软件对筛查到的常见SNP进行LD和单倍型分析。结果共筛查到15个SNP,其中10个为新发现SNP,7个为常见SNP,等位基因频率> 0．05。在3′端的4个SNP存在显著的LD(|D′|>0．75且|D′|的置信区间估计提示强LD,r2>0．33, P<0．031),组成一个明显的单倍型区块;5′端3个SNP间的LD则不明确。结论RDH8基因区域的LD分析结果提示,在进行有关RDH8基因的关联分析时,3′端需要一个代表性SNP位点即可(RDH8ESa也许最为合适),而在5′端则至少需要2个SNP(如RDH851)。Objective As part of an on-going effort to map genes involved in complex eye diseases, myopia in particular, single nucleotide polymorphisms （SNPs） and linkage disequilibrium （LD） pattern were used to identified the gene within and around the AU-trans-retinol dehydrogenase （RDH8）. Methods Denaturing high-performance liquid chromatography （ DHPLC ） was used to screen SNPs in 4 DNA pools each consisting of DNA from five individuals, and genotypes identified SNPs coupled with DNA pooling strategy were performed in 150 Chinese subjects from Hong Kong. The identified common SNPs were included in LD and haplotype analysis using the Haploview2.05 and EH programs. Results Fifteen SNPs were identified ： 7 were common with the minor allele frequency 〉 0. 05, and 10 were novel. Four SNPs in the 3＇ region exhibited significant LD （｜D＇｜ 〉 0. 75 and its confidence interval suggesting strong LD, r^2 〉 0. 33, P〈0. 031 ）and formed a haplotype block while 3 common SNPs in the 5＇ region did not exhibit obvious LD. Conclusion The block-like LD pattern existed around the RDH8 gene region suggest that one SNP （ RDH8E5a probably） in the 3 ＇region and at least 2 SNPs in the 5＇ region （ RDH851 particularly） were needed in association studies involving RDH8.

关 键 词：醇氧化还原酶类 色谱法 高压液相 连锁不平衡 单元型 多态性 单核苷酸 

分 类 号：R77[医药卫生—眼科]