Bates G, Lehrach H
Genome Analysis Laboratory, Imperial Cancer Research Fund, London, UK.
Bioessays. 1994 Apr;16(4):277-84. doi: 10.1002/bies.950160411.
Trinucleotide repeat expansions are now a well-established mutational mechanism in human genetic disease. An unstable CAG repeat is known to be responsible for three neurodegenerative disorders: Huntington's disease, spinal and bulbar muscular atrophy and spinocerebellar ataxia type 1. Similarities in the genetics of these diseases, the size of the repeat expansions and the position of the unstable repeat within the gene (when known) suggest a common basis to the observed phenotypes. The cloning of two regions at which chromosome breakage can be induced (FRAXA and FRAXE) has in each case uncovered an unstable CG-rich triplet repeat which becomes methylated when fully expanded. In addition to these two classes of mutation, the presence of an expanded CTG repeat in the 3' untranslated region of a protein kinase causes myotonic dystrophy. The size of the respective expansions, repeat stability, mutational origins and possible mechanisms of action are discussed.
三核苷酸重复序列扩增现已成为人类遗传疾病中一种公认的突变机制。已知不稳定的CAG重复序列与三种神经退行性疾病有关：亨廷顿舞蹈症、脊髓延髓性肌萎缩症和1型脊髓小脑共济失调。这些疾病在遗传学上的相似性、重复序列扩增的大小以及基因内不稳定重复序列的位置（已知时）表明所观察到的表型具有共同基础。在两个可诱导染色体断裂的区域（FRAXA和FRAXE）进行克隆，在每种情况下都发现了一个富含CG的不稳定三联体重复序列，当完全扩增时会发生甲基化。除了这两类突变外，蛋白激酶3'非翻译区中CTG重复序列的扩增会导致强直性肌营养不良。文中讨论了各自扩增的大小、重复序列稳定性、突变起源及可能的作用机制。
