DNA甲基化(DNAm)在实际年龄确定中的应用在过去几年中已被广泛研究,因为它在法医遗传学领域中的应用。大多数法医研究都是基于血液,唾液,和口腔细胞样本,分别。尽管这些类型的样本代表了在犯罪现场发现的大量痕迹或易于从个人获得,其他组织的样本可能与法医调查有关。年龄确定对于涉及无法识别的身体的病例可能很重要,并且基于剩余的软组织,例如大脑和肌肉,或完全依赖于硬组织,如骨。然而,由于DNAm的细胞类型特异性,尚不清楚细胞类型特异性年龄依赖性CpG位置是否也适用于其他细胞类型的年龄确定。在这项试点研究中,我们调查了之前基于全血分析选择的13个年龄依赖性基因座,包括ELOVL2,TRIM59,F5和KLF14等,在其他法医相关组织中是否也具有预测价值.大脑样本,骨头,肌肉,颊拭子,和29例死亡个体(年龄范围0-87岁)的全血使用大规模平行测序分析了这13种年龄依赖性标志物。这些基因座中的七个在所有五个组织中确实显示出年龄依赖性。DNAm在一生中的变化在分析的一组组织中是不同的,有时基因座内的其他CpG位点显示出较高的年龄依赖性。这项初步研究表明,现有的血液DNAm标记用于年龄确定的潜力,可以分析血液以外的其他组织。我们确定了七个已知的基于血液的DNAm标记用于肌肉,大脑,骨头,颊拭子,还有血.然而,每个组织需要不同的参考集以适应DNAm随时间的组织特异性变化。
The use of DNA methylation (DNAm) for chronological age determination has been widely investigated within the last few years for its application within the field of forensic genetics. The majority of forensic studies are based on blood, saliva, and buccal cell samples, respectively. Although these types of samples represent an extensive amount of traces found at a crime scene or are readily available from individuals, samples from other tissues can be relevant for forensic investigations. Age determination could be important for cases involving unidentifiable bodies and based on remaining soft tissue e.g. brain and muscle, or completely depend on hard tissue such as bone. However, due to the cell type specificity of DNAm, it is not evident whether cell type specific age-dependent CpG positions are also applicable for age determination in other cell types. Within this pilot
study, we investigated whether 13 previously selected age-dependent loci based on whole blood analysis including amongst others ELOVL2, TRIM59, F5, and KLF14 also have predictive value in other forensically relevant tissues. Samples of brain, bone, muscle, buccal swabs, and whole blood of 29 deceased individuals (age range 0-87 years) were analyzed for these 13 age-dependent markers using massive parallel sequencing. Seven of these loci did show age-dependency in all five tissues. The change of DNAm during lifetime was different in the set of tissues analyzed, and sometimes other CpG sites within the loci showed a higher age-dependency. This pilot
study shows the potential of existing blood DNAm markers for age-determination to analyze other tissues than blood. We identified seven known blood-based DNAm markers for use in muscle, brain, bone, buccal swabs, and blood. Nevertheless, a different reference set for each tissue is needed to adapt for tissue-specific changes of the DNAm over time.