Reddy P S, Housman D E
Department of Biology and Center for Cancer Research, Room E17-541, Massachusetts Institute of Technology, 40 Ames Street, Cambridge, MA 02139, USA.
Curr Opin Cell Biol. 1997 Jun;9(3):364-72. doi: 10.1016/s0955-0674(97)80009-9.
The expansion of trinucleotide repeat sequences has now been shown to be the underlying cause of at least ten human disorders. Unifying features among these diseases include the unstable behavior of the triplet repeat during germline transmission when the length of the repeat exceeds a critical value. However, the trinucleotide repeat disorders can be divided into two distinct groups. Type I disorders involve the expansion of CAG repeats, which encode an expanded polyglutamine, inserted into the open-reading frame of a gene that is usually quite broadly expressed. Recently, mouse models for type I disorders have been developed and the basis of pathology is under study, both in these models and through biochemical and cell biological approaches. The type II disorders involve repeat expansions in noncoding regions of genes. The mechanisms by which these repeat expansions lead to pathology may be quite diverse.
现已证明，三核苷酸重复序列的扩增是至少十种人类疾病的根本原因。这些疾病的共同特征包括，当重复序列的长度超过临界值时，三联体重复在种系传递过程中表现出不稳定的特性。然而，三核苷酸重复疾病可分为两个不同的组。I型疾病涉及CAG重复序列的扩增，该序列编码一个扩展的聚谷氨酰胺，插入到一个通常广泛表达的基因的开放阅读框中。最近，已经开发出I型疾病的小鼠模型，并且正在这些模型中以及通过生化和细胞生物学方法研究病理学基础。II型疾病涉及基因非编码区的重复扩增。这些重复扩增导致病理学的机制可能多种多样。
