Trinucleotide repeats associated with human disease
Trinucleotide repeats associated with human disease
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DOI：
10.1093/nar/25.12.2245
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发表时间：
1997-06-15
影响因子：
14.9
通讯作者：
Mitas, M
中科院分区：
文献类型：
--
作者：
Mitas, M
三重重复扩张性疾病(TREDS)的特征是疾病表现与特定基因中包含的d(CAG.CTG)、d(CGG.CCG)或d(GAA.TTC)重复序列的扩增相一致。三联体重复序列的扩增在受影响个体的后代中继续存在，这通常会导致疾病的逐渐严重和/或发病年龄的提前，这一现象在临床上被称为“预期”。最近的生物物理和生化研究表明，与人类疾病相关的6个互补序列中的5个[d(CGG)(N)，d(CCG)(N)，(CAG)(N)，d(CTG)(N)和d(GAA)(N)]形成稳定的发夹结构。虽然三联体重复序列d(GAC)(N)和d(GTC)(N)也形成发夹，但这些序列的双链形式的重复明显地不存在于DNA序列数据库中，并且预计不会与人类疾病相关。除了d(Gag)(N)和d(GTG)(N)外，其余的三联体重复序列在生理盐和温度下不太可能形成发夹结构。总结和讨论了含有三核苷酸重复序列的发夹结构的细节，并讨论了三重重复序列扩展和d(CGG.CCG)(N)甲基化/去甲基化的潜在机制。
Triplet repeat expansion diseases (TREDs) are characterized by the coincidence of disease manifestation with amplification of d(CAG.CTG), d(CGG.CCG) or d(GAA.TTC) repeats contained within specific genes. Amplification of triplet repeats continues in offspring of affected individuals, which generally results in progressive severity of the disease and/or an earlier age of onset, phenomena clinically referred to as 'anticipation'. Recent biophysical and biochemical studies reveal that five of the six [d(CGG)(n), d(CCG)(n), (CAG)(n), d(CTG)(n) and d(GAA)(n)] complementary sequences that are associated with human disease form stable hairpin structures. Although the triplet repeat sequences d(GAC)(n) and d(GTC)(n) also form hairpins, repeats of the double-stranded forms of these sequences are conspicuously absent from DNA sequence databases and are not anticipated to be associated with human disease. With the exception of d(GAG)(n) and d(GTG)(n), the remaining triplet repeat sequences are unlikely to form hairpin structures at physiological salt and temperature. The details of hairpin structures containing trinucleotide repeats are summarized and discussed with respect to potential mechanisms of triplet repeat expansion and d(CGG.CCG)(n) methylation/demethylation.