Molecular Epidemiology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
PLoS One. 2022 Mar 16;17(3):e0261481. doi: 10.1371/journal.pone.0261481. eCollection 2022.
In humans, the nc886 locus is a polymorphically imprinted metastable epiallele. Periconceptional conditions have an effect on the methylation status of nc886, and further, this methylation status is associated with health outcomes in later life, in line with the Developmental Origins of Health and Disease (DOHaD) hypothesis. Animal models would offer opportunities to study the associations between periconceptional conditions, nc886 methylation status and metabolic phenotypes further. Thus, we set out to investigate the methylation pattern of the nc886 locus in non-human mammals.
We obtained DNA methylation data from the data repository GEO for mammals, whose nc886 gene included all three major parts of nc886 and had sequency similarity of over 80% with the human nc886. Our final sample set consisted of DNA methylation data from humans, chimpanzees, bonobos, gorillas, orangutangs, baboons, macaques, vervets, marmosets and guinea pigs.
In human data sets the methylation pattern of nc886 locus followed the expected bimodal distribution, indicative of polymorphic imprinting. In great apes, we identified a unimodal DNA methylation pattern with 50% methylation level in all individuals and in all subspecies. In Old World monkeys, the between individual variation was greater and methylation on average was close to 60%. In guinea pigs the region around the nc886 homologue was non-methylated. Results obtained from the sequence comparison of the CTCF binding sites flanking the nc886 gene support the results on the DNA methylation data.
Our results indicate that unlike in humans, nc886 is not a polymorphically imprinted metastable epiallele in non-human primates or in guinea pigs, thus implying that animal models are not applicable for nc886 research. The obtained data suggests that the nc886 region may be classically imprinted in great apes, and potentially also in Old World monkeys, but not in guinea pigs.
在人类中，nc886 基因座是一个多态性印迹的亚稳定表观等位基因。围孕期条件会影响 nc886 的甲基化状态，并且这种甲基化状态与以后的生活中的健康结果有关，符合健康与疾病的发育起源（DOHaD）假说。动物模型将为进一步研究围孕期条件、nc886 甲基化状态和代谢表型之间的关联提供机会。因此，我们着手研究非人类哺乳动物中 nc886 基因座的甲基化模式。
我们从哺乳动物的 GEO 数据存储库中获取了 DNA 甲基化数据，其中 nc886 基因包含 nc886 的所有三个主要部分，与人类 nc886 的序列相似性超过 80%。我们的最终样本集包括来自人类、黑猩猩、倭黑猩猩、大猩猩、猩猩、狒狒、猕猴、长尾猕猴、绒猴和豚鼠的 DNA 甲基化数据。
在人类数据集，nc886 基因座的甲基化模式遵循预期的双峰分布，表明多态性印迹。在大型猿类中，我们在所有个体和亚种中鉴定出 50%甲基化水平的单峰 DNA 甲基化模式。在旧世界猴中，个体间的变异更大，平均甲基化水平接近 60%。在豚鼠中，nc886 同源物周围的区域是非甲基化的。侧翼 nc886 基因的 CTCF 结合位点的序列比较结果支持 DNA 甲基化数据的结果。
我们的结果表明，与人类不同，nc886 在非人类灵长类动物或豚鼠中不是一个多态性印迹的亚稳定表观等位基因，因此意味着动物模型不适用于 nc886 研究。获得的数据表明，nc886 区域可能在大型猿类中经典印迹，并且可能在旧世界猴中，但不在豚鼠中。
