GGH基因多态性研究及一个新的错义突变T191G的发现
A Novel Missense Mutation(T191G) Identified in y-glutamyl Hydrolase Gene
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摘要:目的 研究γ-谷氨酰水解酶基因(γ-glutamyl hydrolase, GGH)T16C单核苷酸多态性(single nucleotide polymorphism, SNP)在急性白血病(acute leukemia, AL)患儿和正常儿童中的频率分布特征, 并以期发现新的多态性位点。方法 应用DNA直接测序技术, 对90例AL患儿和120例正常儿童的cDNAs进行GGH T16C基因型的筛查。结果 在GGH的第2外显子发现一新的错义突变T191G, 导致第64位氨基酸由亮氨酸(Leu)被色氨酸(Trp)替代。首次鉴定了中国儿童GGH T16C多态性, 其在AL患儿及正常儿童中的等位基因频率分别为20.0%和17.1%, 两组间的等位基因频率差异无统计学意义(P > 0.05), 表明与白血病的易感性无相关性。结论 首次确定了国内汉族儿童GGH T16C的等位基因频率, 并发现一新的错义突变GGHT191G。Abstract:Objective This study aims to investigate the distribution ofγ-glutamyl hydrolase gene(GGH) T16C genotype and allele frequency in children with acute leukemia(AL) and healthy children and to identify the novel single nucleotide polymorphism(SNP).Methods Bone marrow samples from 90 children with AL and peripheral blood samples from 120 healthy children(controls) were obtained to prepare complementary DNA(cDNA).The cDNA was analyzed for the polymorphism in GGH T16C by direct sequencing.Results A novel missense mutation was a T→G transition in the second nucleotide of codon 64 in exon 2 of the GGH gene, which was predicted to result in the substitution of leucine with tryptophan(Leu 64 Trp).The T16C polymorphism in the coding region of the GGH gene was first identified in Chinese children.The T16C allelic frequency in the AL children was 20%, whereas that in the control group was 17.1%. The allelic frequency of SNP was not associated with susceptibility to AL.Conclusion This work is the first report concerning the examination of T16C polymorphism of GGH in Chinese Han children.A novel GGH gene missense mutation T191G was identified in healthy Chinese children.
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