1 School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA.
2 Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA.
Cartilage. 2019 Jul;10(3):335-345. doi: 10.1177/1947603518759173. Epub 2018 Feb 19.
Osteoarthritis (OA) affects humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA.
Trabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, 5 with and 5 without knee OA. The Infinium HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation patterns in these tissues.
Approximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the 2 filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues.
Overall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.
骨关节炎(OA)影响人类和其他几种动物。因此,这种疾病的机制,如特定的骨骼组织 DNA 甲基化模式,可能是进化保守的。然而,甲基化与 OA 之间的关联尚未在非人类动物中得到充分研究。狒狒是疾病的重要模型,其 OA 发生率与人类相似。因此,本研究调查了狒狒甲基化与 OA 之间的关联,以推进对 OA 的进化理解。
从成年雌性狒狒股骨内侧髁采集骨小梁和软骨,其中 5 例有膝 OA,5 例无膝 OA。使用 Infinium HumanMethylation450 BeadChip(450K 芯片)来鉴定这些组织中的 DNA 甲基化模式。
大约 44%的 450K 芯片探针可靠地与狒狒基因组匹配,包含感兴趣的 CpG 位点,并且在整个基因组中保持广泛的分布。在测试的 2 种过滤方法中,都在软骨组织中鉴定出健康和 OA 个体之间存在显著差异甲基化位置(DMPs),其中一些模式与之前在人类中鉴定出的模式重叠。相反,在骨组织中,在组织类型之间或疾病状态之间均未发现 DMPs。
总体而言,450K 芯片可用于测量狒狒组织中的全基因组 DNA 甲基化,并识别与复杂性状的显著关联。本研究的结果表明,与 OA 相关的一些 DNA 甲基化模式是进化保守的,而另一些则不是。这需要在更大、更系统发育多样化的样本集中进一步研究。