Department of Forensic Medicine, Faculty of Medicine, University of Granada, Avda. de la Investigación, 11, 18016, Granada, Spain.
Department of Statistics, Faculty of Medicine, University of Granada, Avda. de la Investigación, 11, 18016, Granada, Spain.
Int J Legal Med. 2020 Mar;134(2):451-459. doi: 10.1007/s00414-019-02242-7. Epub 2020 Jan 2.
In the last decade, increasing knowledge of epigenetics has led to the development of DNA methylation-based models to predict age, which have shown high predictive accuracy. However, despite the value of teeth as forensic samples, few studies have focused on this source of DNA. This study used bisulfite pyrosequencing to measure the methylation levels of specific CpG sites located in the ELOVL2, ASPA, and PDE4C genes, with the aim of selecting the most age-informative genes and determining their associations with age, in 65 tooth samples from individuals 15 to 85 years old. As a second aim, methylation data and measurements of relative telomere length in the same set of samples were used to develop preliminary age prediction models to evaluate the accuracy of both biomarkers together and separately in estimating age from teeth for forensic purposes. In our sample, several CpG sites from ELOVL2 and PDE4C genes, as well as telomere length, were significantly associated with chronological age. We developed age prediction quantile regression models based on DNA methylation levels, with and without telomere length as an additional variable, and adjusted for type of tooth and sex. Our results suggest that telomere length may have limited usefulness as a supplementary marker for DNA methylation-based age estimation in tooth samples, given that it contributed little improvement in the prediction errors of the models. In addition, even at older ages, DNA methylation appeared to be more informative in predicting age than telomere length when both biomarkers were evaluated separately.
在过去的十年中,人们对表观遗传学的认识不断增加,这导致了基于 DNA 甲基化的模型的发展,以预测年龄,这些模型已经显示出了很高的预测准确性。然而,尽管牙齿作为法医样本具有很高的价值,但很少有研究关注这种 DNA 来源。本研究使用亚硫酸氢盐焦磷酸测序来测量位于 ELOVL2、ASPA 和 PDE4C 基因中的特定 CpG 位点的甲基化水平,目的是选择最具年龄信息的基因,并确定它们与年龄的关系,研究对象是 65 颗来自 15 至 85 岁个体的牙齿样本。本研究的第二个目的是,使用相同样本中的甲基化数据和相对端粒长度测量值,开发初步的年龄预测模型,以评估这两种生物标志物在用于法医目的时,共同和分别从牙齿估计年龄的准确性。在我们的样本中,ELOVL2 和 PDE4C 基因中的几个 CpG 位点以及端粒长度与实际年龄显著相关。我们开发了基于 DNA 甲基化水平的年龄预测分位数回归模型,包括和不包括端粒长度作为附加变量,并根据牙齿类型和性别进行了调整。我们的结果表明,考虑到端粒长度对模型预测误差的改善贡献很小,因此它可能作为基于 DNA 甲基化的年龄估计在牙齿样本中补充标记物的作用有限。此外,即使在年龄较大时,当单独评估这两种生物标志物时,DNA 甲基化在预测年龄方面似乎比端粒长度更具信息量。