Universal newborn screening (NBS) is a highly successful public health intervention. Archived dried bloodspots (DBS) collected for NBS represent a rich resource for population genomic studies. To fully harness this resource in such studies, DBS must yield high-quality genomic DNA (gDNA) for whole genome sequencing (WGS). In this pilot study, we hypothesized that gDNA of sufficient quality and quantity for WGS could be extracted from archived DBS up to 20 years old without PCR (Polymerase Chain Reaction) amplification. We describe simple methods for gDNA extraction and WGS library preparation from several types of DBS. We tested these methods in DBS from 25 individuals who had previously undergone diagnostic, clinical WGS and 29 randomly selected DBS cards collected for NBS from the California State Biobank. While gDNA from DBS had significantly less yield than from EDTA blood from the same individuals, it was of sufficient quality and quantity for WGS without PCR. All samples DBS yielded WGS that met quality control metrics for high-confidence variant calling. Twenty-eight variants of various types that had been reported clinically in 19 samples were recapitulated in WGS from DBS. There were no significant effects of age or paper type on WGS quality. Archived DBS appear to be a suitable sample type for WGS in population genomic studies.

新生儿普查 (NBS) 是一项非常成功的公共卫生干预措施。为 NBS 收集的存档干血斑 (DBS) 代表了群体基因组研究的丰富资源。为了在此类研究中充分利用这一资源，DBS 必须为全基因组测序 (WGS) 生成高质量的基因组 DNA (gDNA)。在这项初步研究中，我们假设可以从长达 20 年的存档 DBS 中提取质量和数量足以用于 WGS 的 gDNA，而无需 PCR（聚合酶链反应）扩增。我们描述了从几种类型的 DBS 中提取 gDNA 和 WGS 文库的简单方法。我们在 DBS 中测试了这些方法，这些人来自 25 名以前接受过诊断、临床 WGS 的人，以及从加利福尼亚州生物银行为 NBS 收集的 29 张随机选择的 DBS 卡。虽然来自 DBS 的 gDNA 的产量明显低于来自同一个体的 EDTA 血液，但它的质量和数量足以用于无需 PCR 的 WGS。所有样本 DBS 产生的 WGS 均符合高置信度变异检出的质量控制指标。在 DBS 的 WGS 中概括了 19 个样本中临床报告的各种类型的 28 种变体。年龄或纸张类型对 WGS 质量没有显着影响。存档的 DBS 似乎是群体基因组研究中 WGS 的合适样本类型。在 DBS 的 WGS 中概括了 19 个样本中临床报告的各种类型的 28 种变体。年龄或纸张类型对 WGS 质量没有显着影响。存档的 DBS 似乎是群体基因组研究中 WGS 的合适样本类型。在 DBS 的 WGS 中概括了 19 个样本中临床报告的各种类型的 28 种变体。年龄或纸张类型对 WGS 质量没有显着影响。存档的 DBS 似乎是群体基因组研究中 WGS 的合适样本类型。