AN UNSTABLE TRIPLET REPEAT IN A GENE RELATED TO MYOTONIC MUSCULAR-DYSTROPHY
AN UNSTABLE TRIPLET REPEAT IN A GENE RELATED TO MYOTONIC MUSCULAR-DYSTROPHY
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DOI：
10.1126/science.1546326
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发表时间：
1992-03-06
期刊：
影响因子：
56.9
通讯作者：
CASKEY, CT
中科院分区：
文献类型：
--
作者：
FU, YH;PIZZUTI, A;CASKEY, CT
在扫描策略中使用含有富含 GC 的三联体序列的合成寡核苷酸来识别强直性肌营养不良 (DM) 基因座的不稳定基因序列。高度多态性的 GCT 重复被发现并不稳定，DM 患者中重复次数增加。在严重先天性糖尿病的情况下，父亲的三联体等位基因未改变地遗传，而母亲的糖尿病相关等位基因则不稳定。这些研究表明，导致 DM 的突变机制是三联体扩增，类似于脆性 X 综合征中发生的情况。三联体重复序列位于基因（称为肌强直蛋白激酶）内，该基因具有与蛋白激酶相似的序列。
Synthetic oligonucleotides containing GC-rich triplet sequences were used in a scanning strategy to identify unstable genetic sequences at the myotonic dystrophy (DM) locus. A highly polymorphic GCT repeat was identified and found to be unstable, with an increased number of repeats occurring in DM patients. In the case of severe congenital DM, the paternal triplet allele was inherited unaltered while the maternal, DM-associated allele was unstable. These studies suggest that the mutational mechanism leading to DM is triplet amplification, similar to that occurring in the fragile X syndrome. The triplet repeat sequence is within a gene (to be referred to as myotonin-protein kinase), which has a sequence similar to protein kinases.