脆性X综合征中不稳定的DNA序列和异常甲基化研究

采用ＰＣＲ结合序列胶分析的方法，对８２条正常中国人Ｘ染色体ＦＲＡＸＡ位点（ＣＧＧ）ｎ重复序列拷贝数的多态性进行了测定，其范围为２１～３１，高峰为２７。并通过Ｓｏｕｔｈｅｒｎ杂交分析了来自６个Ｆｒａ（Ｘ）家系的１５名成员（ＣＧＧ）ｎ的拷贝数与该重复序列上游ＣｐＧ岛的甲基化状态。Ｆｒａ（Ｘ）患者（ＣＧＧ）ｎ大量扩增并伴随ＣｐＧ岛异常甲基化。Ｆｒａ（Ｘ）携带者女性（ＣＧＧ）ｎ扩增较少，有嵌合现象。其子代或产生更大扩增，或保持原来状态，呈动态突变遗传特征。

Unstable DNA sequence and methylation in fragile Xsyndrome

ragile X syndrome is characterized as an inherit-ed unstable DNA sequence: the increasement of(CGG)n copy number.It sufferred from the inactiva-tion of FMR-1 (fragile X mental retardation 1 ). whichis inhibited by arnplification of (CGC)n and methyla-tion of CpG island. The (CGG)n repeat variation innormal Chinese population was detected by PCR withsequencuig gel analysis. We also analysed the amplifi-cation of (CGG) n and methylation of CpG island atXq27.3 from 15 individuals in 6 families by Southernhybridization. These results indicate that abnormalmethyiation of CpG island always occurs in Fra (X)Patients together with large amplification of (CGG)n.The (CGG )n could be erther stable or amplified in off-springs of carrier females.These suggest that therewould be a newgenetic mechanism:dynamic mutation.