Kremer E J, Pritchard M, Lynch M, Yu S, Holman K, Baker E, Warren S T, Schlessinger D, Sutherland G R, Richards R I
Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, South Australia.
Science. 1991 Jun 21;252(5013):1711-4. doi: 10.1126/science.1675488.
The sequence of a Pst I restriction fragment was determined that demonstrate instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG)n. The sequence 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.
确定了一个Pst I限制性片段的序列，该序列在脆性X综合征家系中显示出不稳定性。不稳定性区域定位于三核苷酸重复序列p(CCG)n。该重复序列两侧的序列在正常个体和患病个体中是相同的。为在脆性位点断裂而构建的两个体细胞杂种中的断点也定位于此重复序列。该重复序列在非同源宿主中克隆时以及通过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是不稳定性以及可能的脆性位点的分子基础。这将解释该区域在体内和体外观察到的特性。
