Department of Anthropology, University of Washington, Seattle, Washington, USA.
Department of Anthropology, Emory University, Atlanta, Georgia, USA.
Am J Hum Biol. 2021 Jan;33(1):e23410. doi: 10.1002/ajhb.23410. Epub 2020 Mar 18.
Telomeres are the protective caps of chromosomes. They shorten with cell replication, age, and possibly environmental stimuli (eg, infection and stress). Short telomere length (TL) predicts subsequent worse health. Although venous whole blood (VWB) is most commonly used for TL measurement, other, more minimally invasive, sampling techniques are becoming increasingly common due to their field-friendliness, allowing for feasible measurement in low-resource contexts. We conducted statistical validation work for measuring TL in dried blood spots (DBS) and incorporated our results into a meta-analysis evaluating minimally invasive sampling techniques to measure TL.
We isolated DNA extracts from DBS using a modified extraction protocol and tested how they endured different shipping conditions and long-term cryostorage. We then included our in-house DBS TL validation statistics (correlation values with VWB TL and age) in a series of meta-analyses of results from 24 other studies that published similar associations for values between TL measured in DBS, saliva, and buccal cells.
Our modified DBS extraction technique produced DNA yields that were roughly twice as large as previously recorded. Partially extracted DBS DNA was stable for 7 days at room temperature, and still provided reliable TL measurements, as determined by external validation statistics. In our meta-analysis, DBS TL had the highest external validity, followed by saliva, and then buccal cells-possibly reflecting similarities/differences in cellular composition vs VWB.
DBS DNA is the best proxy for VWB from the three minimally-invasively specimen types evaluated and can be used to expand TL research to diverse settings and populations.
端粒是染色体的保护帽。它们随着细胞复制、衰老以及可能的环境刺激（例如感染和压力）而缩短。端粒长度较短预示着随后的健康状况恶化。尽管静脉全血（VWB）是最常用于测量端粒长度的方法，但由于其便于在现场使用，其他更微创的采样技术由于其便于现场使用，在低资源环境中进行可行的测量，因此越来越普遍。我们对测量干燥血斑（DBS）中的端粒长度进行了统计验证工作，并将我们的结果纳入了一项评估微创采样技术以测量端粒长度的荟萃分析中。
我们使用改良的提取方案从 DBS 中分离 DNA 提取物，并测试了它们如何承受不同的运输条件和长期冷冻储存。然后，我们将我们内部的 DBS 端粒长度验证统计数据（与 VWB 端粒长度和年龄的相关值）纳入一系列荟萃分析中，这些分析汇总了其他 24 项研究的结果，这些研究发表了关于 DBS、唾液和口腔细胞中测量的端粒长度之间相似关联的结果。
我们改良的 DBS 提取技术产生的 DNA 产量大约是之前记录的两倍。部分提取的 DBS DNA 在室温下稳定 7 天，并且仍然可以提供可靠的 TL 测量值，这是通过外部验证统计数据确定的。在我们的荟萃分析中，DBS TL 的外部有效性最高，其次是唾液，然后是口腔细胞，这可能反映了细胞成分与 VWB 的相似性/差异。
在评估的三种微创标本类型中，DBS DNA 是与 VWB 最接近的替代物，可以用于将 TL 研究扩展到不同的环境和人群。
