Going retro
Going retro
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复古风
DOI：
10.1038/nm.3475
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发表时间：
2014
期刊：
影响因子：
82.9
通讯作者：
Eva Chmielnicki
中科院分区：
文献类型：
--
作者：
Eva Chmielnicki
反转录转座子是在整个基因组中发现的可移动的遗传元件。新的反转录转座子拷贝插入或附近的基因可能参与疾病的发病机制。现在，三木Bundo和同事已经确定了高拷贝数的逆转录转座子L1，特别是在精神分裂症患者与正常对照组和其他精神疾病患者相比的死后前额叶皮层神经元中（Neuron doi：10.1016/j. neuron. 2013.10. 053，2014年1月2日）。通过对精神分裂症患者和对照组的脑DNA进行全基因组测序，作者发现精神分裂症患者的L1插入位点经常出现在与神经元和突触功能相关的基因中或附近。从机制上讲，免疫刺激剂poly-I：C激活怀孕小鼠的母体免疫，导致后代L1拷贝数增加。研究结果表明，早期环境风险因素（以前与疾病风险增加有关）如何驱动遗传变化，导致精神分裂症或其他疾病的发病机制。EC
Retrotransposons are movable genetic elements that are found throughout the genome. Insertion of new retrotransposon copies in or near genes could be involved in disease pathogenesis. Now, Miki Bundo and colleagues have identified a high copy number of the retrotransposon L1 specifically in neurons within the postmortem prefrontal cortex from individuals with schizophrenia compared to normal controls and other psychiatric diseases (Neuron doi: 10.1016/j. neuron. 2013.10. 053, 2 January 2014). Using whole-genome sequencing of brain DNA from the patients with schizophrenia versus control subjects, the authors found that L1 insertions sites in individuals with schizophrenia often occur in or near genes linked to neuronal and synaptic function.Mechanistically, maternal immune activation in pregnant mice with the immunostimulant poly-I: C led to increased L1 copy number in the offspring. The findings suggest how early environmental risk factors, which have been previously linked to increased disease risk, could drive genetic changes that contribute to the pathogenesis of schizophrenia or other illnesses.—EC