遗传性痉挛性截瘫基因SPG3A的基因组结构和多态性分析

目的:分析遗传性痉挛性截瘫(HSP)SPG3A基因组结构,探讨部分正常人群SPG3A的基因多态性。方法:应用DNA序列测定对110个年龄大于60岁的正常人进行SPG3A/Atlastin基因多态分析。结果:在外显子2和外显子3的编码序列中有两处基因多态;内含子3,内含子4和内含子6上分别发现了一处基因多态。结论:正常个体的等位基因中发现只有2个编码序列多态性且为高度保留序列,其余3个均位于内含子上。对序列变异、多态性相对频率及SPG3A基因组结构的分析将有助于遗传性痉挛性截瘫疾病和其它轴突变性神经疾病的遗传分析。

Genomic Organization and Polymorphism Analysis of Hereditary Spastic Paraplegia Gene, SPG3A

Objective: To analyze the HSP/SPG3A genomic structure and polymorphism in some normal subjects.Methods: Polymorphism analysis of hereditary spastic paraplegia(HSP) gene,SPG3A among 110 normal subjects was carried out by 3 100 genetic analyzer and DNAstar software.Results: Polymorphisms were identified in exon 2(A to G substitution at cDNA position 84) and exon 3(A to G substitution at cDNA position 351).They also revealed a T to G substitution in intron 3,an A to C substitution in intron 4,and a G to A substitution in intron 6.Conclusion: Polymorphisms analysis of 96 to 192 SPG3A alleles in control subjects revealed only two coding sequence polymorphisms,both of which were conserved.Neither of these nucleotide changes altered predicted amino acids.Nonetheless,it is important for investigators to be aware of these sequence variants as they are relatively frequent.Understanding SPG3A's genomic organization and polymorphism content will facilitate its analysis in HSP and other degenerative neurological disorders.