脆性X综合征FMR1基因AGG排布式分析

Analysis of AGG interspersion of the FMR1 gene in fragile X syndrome

目的研究中国正常人群FMR1基因与其不稳定扩增相关的（CGG）n重复序列的多态性及AGG排布式。方法应用AmplideX FMR1 PCRKit试剂盒扩增随机选取的380条x染色体，其中男性176例，女性102例，将11例脆性x综合征前突变携带者、10例脆性X综合征全突变患者作为阳性对照，用GeneMapperV4．0软件分析毛细管电泳结果，用SPSS11．0软件进行数据分析。结果女性样本杂合子比例为64．70％。在正常男性和女性样本中检测到的等位基因数分别为15和14种，AGG排布式为26和27种，男性（CGG）n重复数范围为17～45，女性为2l～44，其中1例为灰区携带者。男性和女性最大频率等位基因数均为29，其次为30、36，（CGG）n重复数为28的等位基因缺如。AGG排布式以9A9A9最常见。在正常人群中，99．21％有不同形式和数目的AGG嵌入，其中6A嵌入模块所占的比例高达10．02％，且多分布在较大的重复数片段中，而57．58％对照样本无AGG嵌入，且无1例患者样本有6A嵌入。正常男性、女性（CGG）n重复数的频数分布、AGG排布式差异均无统计学意义（P〉0．05），AGG数目在正常人群与对照间差异有统计学意义（P〈0．05）。结论AGG数目及排布式可能对保持中国大陆人群（CGG）n稳定性有重要的意义，9A9A6A9可能为亚洲人群阻止（CGG）n不稳定扩增的一种特殊的排布式。

Objective To analyze （CGG）n repeats sequence and AGG interspersion correlated with unstable expansion of FMRI gene in a general Chinese population. Methods AmplideX FMR1 PCR Kit was used to amplify 380 X chromosomes from randomly selected 176 males and 102 females, 11 permutation carriers and 10 full mutation patients have served as controls. Results of capillary electrophoresis were analyzed with GeneMapper software Version 4. 0. SPSS 11. 0 software was used for statistical analysis. Results The ratio of heterozygous females was 64.70%. The number of alleles in general males and females was 15 and 14, the classes of AGG pattern was 26 and 27, respectively. The range of alleles was between 17-45 CGG repeats in males and 21-44 CGG repeats in females, and 1 male was identified as gray zone carrier. The most frequent allele was 29 CGG repeats, which was followed by 30 and 36 repeats, while 28 CGG repeats were absent. The most common AGG pattern was 9AgA9, 99. 21% of the population was detected with different forms and numbers of AGG interruption, and 6A interruption pattern was found in 10.02%samples especially in individuals with more CGG repeats. However, 57.58% of control samples had no AGG interruption, and none of the controls had 6A interruption pattern. No significant difference was observed in allele frequent distribution of （CGG）n repeats and AGG interspersion patterns between the males and females （P 〉 0. 05）, and AGGs was significantly different between general population and controls （P〈0.05）. Conclusion AGGs and AGG pattern may have important roles in maintaining （CGG）n stability in general population of China, 9AgA6A9 may be a special pattern for preventing （CGG）n unstable expansion in Asian populations.