MAPPING OF DNA INSTABILITY AT THE FRAGILE-X TO A TRINUCLEOTIDE REPEAT SEQUENCE P(CCG)N
MAPPING OF DNA INSTABILITY AT THE FRAGILE-X TO A TRINUCLEOTIDE REPEAT SEQUENCE P(CCG)N
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DOI：
10.1126/science.1675488
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发表时间：
1991-06-21
期刊：
影响因子：
56.9
通讯作者：
RICHARDS, RI
中科院分区：
文献类型：
--
作者：
KREMER, EJ;PRITCHARD, M;RICHARDS, RI
在脆性X综合征谱系中，确定了一个Pst I限制性片段的序列，证明了该片段的不稳定性。不稳定区域定位于三核苷酸重复序列p(CCG)n。这个重复序列两侧的序列在正常和患病个体中是相同的。在脆弱位点构建的两个体细胞杂交体的断点也映射到这个重复序列。该重复序列在非同源宿主中克隆和经聚合酶链反应扩增后均表现出不稳定性。这些结果表明，三核苷酸重复拷贝数的变化可能是不稳定和脆弱位点的分子基础。这将解释该区域在体内和体外观察到的特性。
The sequence of a Pst I restriction fragment was determined that demonstrates instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG)n. The sequences flanking this repeat were identical in normal and affected individuals. The breakpoints in two somatic cell hybrids constructed to break at the fragile site also mapped to this repeat sequence. The repeat exhibits instability both when cloned in a nonhomologous host and after amplification by the polymerase chain reaction. These results suggest variation in the trinucleotide repeat copy number as the molecular basis for the instability and possibly the fragile site. This would account for the observed properties of this region in vivo and in vitro.