校准死后时钟的新方法?
来自阿拉巴马州立大学和华盛顿州立大学的研究小组使用了两种动物模型来验证他们的假设。他们使用了斑马鱼和小鼠。通过在不同的时间点,在受控条件下摧毁实验对象,他们试图发现基因上调的速度是否与死亡时间相关。
这并不是第一次对遗传物质进行检测,以确定是否可以计算 PMI。以前的研究利用信使核糖核酸(mRNA)降解来阐明死亡时间。然而,测量特定 mRNA 的降解率有两大缺陷,会产生偏差和不准确性;首先,需要进行聚合酶链反应来扩增 mRNA 的数量;其次,为了比较样本,必须将数据与对照样本进行归一化。
为了消除与测量 mRNA 降解相关的误差,研究小组于 2011 年开发了 "基因测量仪"。基因测量仪能精确测定给定生物样本中特定基因的丰度(无需扩增),还能消除传统 DNA 微阵列中的 "噪音 "造成的误差。基因检测仪的校准方法与 pH 计使用缓冲液校准的方法相同,这意味着在比较样本时无需对校准探针进行归一化处理,而且微阵列信号的非线性性质也会被考虑在内。
利用基因表方法,研究小组发现斑马鱼的548个基因和小鼠的515个基因在死亡后明显不受调控。大部分不受调控的基因位于大脑中。这些基因在死后不受调控的时间差别很大,有些基因在死后48小时达到峰值。研究小组设法证明,利用斑马鱼和小鼠肝脏中发现的基因可以预测死亡时间。大脑基因分析并未显示出与死亡时间的相关性。
这项研究的结果很有见地,也很耐人寻味。未来利用人类尸体进行的研究可能会开发出一种 PMI,以确定拟用于移植的器官的质量。从本质上讲,基因表方法最大限度地减少了使用遗传物质预测PMI的不准确性。
参考文献
- 利用基因表表达数据的线性回归分析准确预测死后间隔时间 M 科尔比-亨特、亚历山大-波日特科夫、彼得-安东尼-诺贝尔 bioRxiv 058370; doi: http://dx.doi.org/10.1101/058370
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