Selection in blood cells from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation.
Selection in blood cells from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation.
复制标题
脆性 X 综合征女性携带者血细胞的选择：年龄与携带完全突变的活跃 X 染色体比例之间呈负相关。
作者：
F. Rousseau;D. Heitz;I. Oberle;J. Mandel
我们研究了脆性X突变女性携带者的突变和X失活模式，试图将它们与各种表型特征联系起来。我们使用了一种简单的检测方法，它同时显示了突变的大小，甲基化状态，以及代表正常活性和非活性X染色体的DNA片段。我们已经观察到一个年龄依赖性的过程，即“完整的”脆性X突变被发现优先在成年女性的白细胞中的非活性X，但在年轻的。这种现象没有观察到女性携带者的“前突变”，谁有很少的表型表达。初步数据表明，年轻女性谁表现出优先存在于白细胞中的活性X的完整突变可能会增加精神发育迟滞的风险。我们还获得了初步证据，年龄依赖性减少体细胞异质性的完整突变，可能是由于选择较小的突变片段。如果得到证实，后一种现象可能解释了脆性位点表达随年龄增长而减少的已知现象。我们的观察结果表明，一个基因的表达是由一个完整的突变（可能是FMR-1基因）的存在下，白细胞具有细胞自主功能，导致一个缓慢的渐进选择的细胞突变是在失活的X染色体。
We have studied the patterns of mutation and X inactivation in female carriers of a fragile X mutation, to try to correlate them with various phenotypic features. We used a simple assay, which shows simultaneously the size of the mutation, its methylation status, and DNA fragments that represent the normal active and inactive X chromosomes. We have observed an age dependent process, whereby the 'full' fragile X mutation is found preferentially on the inactive X in leucocytes in adult females, but not in younger ones. This phenomenon was not observed in female carriers of a 'premutation', who have little phenotypic expression. Preliminary data suggest that young females who show preferential presence of a full mutation on the active X in leucocytes may be at increased risk for mental retardation. We have also obtained preliminary evidence for an age dependent decrease in the somatic heterogeneity of full mutations, possibly owing to selection for smaller mutated fragments. If confirmed, the latter phenomenon might account for the known decrease with age of the expression of the fragile site. Our observations suggest that a gene whose expression is affected by the presence of a full mutation (possibly the FMR-1 gene) has a cell autonomous function in leucocytes, leading to a slowly progressive selection for cells where the mutation is on the inactive X chromosome.
脆性 X 综合征：关于表型分子机制的假设。
DOI：
10.1002/ajmg.1320300169
发表时间：
1988
期刊：
American journal of medical genetics
影响因子：
--
作者：
Warren,ST
通讯作者：
Warren,ST