Mohmood Sameena, Sherwani Asma, Khan Fauzia, Khan Rizwan H, Azfer Asim
Section of Genetics, Department of Zoology, AMU, Aligarh, India.
Med Sci Monit. 2003 Sep;9(9):RA237-45.
Dynamic mutations in human genes result from unstable trinucleotide repeats which are expanded within the genome. These expansions of trinucleotide repeats have been shown to be the etiological factors in various neuropsychiatric diseases and other genetic disorders. This hypothesis is supported by various independent studies showing large expansion of trimeric repeats, such as CAG/CTG/CCG/CGG/AAG, in patient DNA samples. These repeats are also identified in other disease loci not clearly related to particular diseases, which indicates that such expansions are one of the general forms of evolution occurring throughout the human genome. The trinucleotide repeat expansions occur during meiosis and are generally irreversible. Accumulation of these repeats over generations eventually ends in a deficiency of replication. There is evidence that certain ethnic groups in the human population have predispositions for expanded repeats related to neuropsychiatric diseases. It is likely that racial/ethnic differences reflect variations, which suggests the possibility of an underlying complex biological process. The present review highlights the importance of repeat expansions in some neuropsychiatric diseases, such as spinal and bulbular atrophy (SBMA), spinocerebellar ataxia (SCA), Huntington's disease (HD), schizophrenia, myotonic dystrophy (DM) and fragile-X syndrome.
人类基因中的动态突变源于基因组内不稳定的三核苷酸重复序列的扩增。这些三核苷酸重复序列的扩增已被证明是多种神经精神疾病和其他遗传疾病的病因。这一假说得到了各种独立研究的支持，这些研究表明，在患者的DNA样本中，三聚体重复序列（如CAG/CTG/CCG/CGG/AAG）有大量扩增。在其他与特定疾病无明显关联的疾病位点也发现了这些重复序列，这表明这种扩增是整个人类基因组中普遍存在的进化形式之一。三核苷酸重复序列的扩增发生在减数分裂过程中，且通常是不可逆的。这些重复序列在几代人中的积累最终会导致复制缺陷。有证据表明，人类中的某些种族群体易发生与神经精神疾病相关的重复序列扩增。种族差异很可能反映了变异，这表明可能存在潜在的复杂生物学过程。本综述强调了重复序列扩增在某些神经精神疾病中的重要性，如脊髓延髓肌萎缩症（SBMA）、脊髓小脑共济失调（SCA）、亨廷顿舞蹈症（HD）、精神分裂症、强直性肌营养不良症（DM）和脆性X综合征。
