TRINUCLEOTIDE REPEAT AMPLIFICATION AND HYPERMETHYLATION OF A CPG ISLAND IN FRAXE MENTAL-RETARDATION
TRINUCLEOTIDE REPEAT AMPLIFICATION AND HYPERMETHYLATION OF A CPG ISLAND IN FRAXE MENTAL-RETARDATION
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DOI：
10.1016/0092-8674(93)90300-f
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发表时间：
1993-07-16
期刊：
影响因子：
64.5
通讯作者：
DAVIES, KE
中科院分区：
文献类型：
--
作者：
KNIGHT, SJL;FLANNERY, AV;DAVIES, KE
我们已经克隆了脆性位点FRAXE，并证明具有该脆性位点的个体具有与人类X染色体Xq 28中的CpG岛相邻的GCC重复序列的扩增。正常个体具有6-25个拷贝的GCC重复序列，而智力迟钝的FRAXE阳性个体具有>200个拷贝，并且在CpG岛也具有甲基化。这种情况类似于FRAXA基因座，是三核苷酸重复扩增与人类遗传疾病相关的另一个例子。与脆性X综合征相比，GCC重复序列可以扩展或收缩，并且在通过男性或女性线路时同样不稳定。这些结果也对理解染色体的脆弱性有影响。
We have cloned the fragile site FRAXE and demonstrate that individuals with this fragile site possess amplifications of a GCC repeat adjacent to a CpG island in Xq28 of the human X chromosome. Normal individuals have 6-25 copies of the GCC repeat, whereas mentally retarded, FRAXE-positive individuals have >200 copies and also have methylation at the CpG island. This situation is similar to that seen at the FRAXA locus and is another example in which a trinucleotide repeat expansion is associated with a human genetic disorder. In contrast with the fragile X syndrome, the GCC repeat can expand or contract and is equally unstable when passed through the male or female line. These results also have implications for the understanding of chromosome fragility.