Dynamic behavior of fragile X full mutations in cultured female fetal fibroblasts  

作　　者：Yu-jieSUN XiaoHAN 

机构地区：[1]LaboratoryofFunctionalGenomicsatNanjingMedicalUniversity,Nanjing210029,China [2]LeslieandSusanGonda（Goldschmied）DiabetesandGeneticsResearchCenter,CityofHopeNationalMedicalCenter,Duarte,California

出　　处：《Acta Pharmacologica Sinica》2004年第7期973-976,共4页中国药理学报（英文版）

摘　　要：AIM: To assess mitotic stability of the fragile X full mutations and itsrelationship with DNA methylation. METHODS: The length change of the expanded CGG repeats wasexamined and correlated it with the methylation status in the DNA samples isolated from thefibroblasts derived from a fragile X female fetus and a fragile X male adult, respectively. RESULTS:A dramatic instability of the expanded CGG repeats in the female fetal fibroblasts was observed.Southern blot analysis revealed that the 6.9-kb major expanded band detected in passage 2 wascompletely replaced by a 7.7-kb band after passage 30. Fibroblast clones derived from the passage 3displayed an unstable expansion of the CGG repeat during clonal proliferation, while methylationstatus of the CGG repeat region was maintained. In contrast, in fragile X male fibroblasts theexpanded CGG repeats were stable during clonal proliferation. CONCLUSION: The mitotic instability ofexpanded CGG repeat is not always restricted in early development window as proposed previously andother elements rather than DNA methylation could affect the stability of the expanded CGG repeatsin fragile X female fetal fibroblast cells.AIM: To assess mitotic stability of the fragile X full mutations and itsrelationship with DNA methylation. METHODS: The length change of the expanded CGG repeats wasexamined and correlated it with the methylation status in the DNA samples isolated from thefibroblasts derived from a fragile X female fetus and a fragile X male adult, respectively. RESULTS:A dramatic instability of the expanded CGG repeats in the female fetal fibroblasts was observed.Southern blot analysis revealed that the 6.9-kb major expanded band detected in passage 2 wascompletely replaced by a 7.7-kb band after passage 30. Fibroblast clones derived from the passage 3displayed an unstable expansion of the CGG repeat during clonal proliferation, while methylationstatus of the CGG repeat region was maintained. In contrast, in fragile X male fibroblasts theexpanded CGG repeats were stable during clonal proliferation. CONCLUSION: The mitotic instability ofexpanded CGG repeat is not always restricted in early development window as proposed previously andother elements rather than DNA methylation could affect the stability of the expanded CGG repeatsin fragile X female fetal fibroblast cells.

关 键 词：DNA FEMALE FETUS FIBROBLASTS fragile X syndrome HETEROZYGOTE human mutation X chromosome 

分 类 号：R714.15[医药卫生—妇产科学]