Department of Biostatistics, School of Public Health, Boston University, Boston, MA, 02118, USA.
School of Medicine, Boston University, Boston, MA, 02118, USA.
Sci Rep. 2022 Feb 2;12(1):1801. doi: 10.1038/s41598-022-05814-7.
Lymphoblastoid cell lines (LCLs) provide an unlimited source of genomic DNA for genetic studies. Here, we compared mtDNA sequence variants, heteroplasmic or homplasmic, between LCL (sequenced by mitoRCA-seq method) and whole blood samples (sequenced through whole genome sequencing approach) of the same 130 participants in the Framingham Heart Study. We applied harmonization of sequence coverages and consistent quality control to mtDNA sequences. We identified 866 variation sites in the 130 LCL samples and 666 sites in the 130 blood samples. More than 94% of the identified homoplasmies were present in both LCL and blood samples while more than 70% of heteroplasmic sites were uniquely present either in LCL or in blood samples. The LCL and whole blood samples carried a similar number of homoplasmic variants (p = 0.45) per sample while the LCL carried a greater number of heteroplasmic variants than whole blood per sample (p < 2.2e-16). Furthermore, the LCL samples tended to accumulate low level heteroplasmies (heteroplasmy level in 3-25%) than their paired blood samples (p = 0.001). These results suggest that cautions should be taken in the interpretation and comparison of findings when different tissues/cell types or different sequencing technologies are applied to obtain mtDNA sequences.
淋巴母细胞系 (LCL) 为遗传研究提供了无限的基因组 DNA 来源。在这里，我们比较了 130 名弗雷明汉心脏研究参与者的 LCL（通过 mitoRCA-seq 方法测序）和全血样本（通过全基因组测序方法测序）之间的线粒体 DNA 序列变异，包括异质性或同质性。我们应用了序列覆盖范围的协调和一致的质量控制来处理 mtDNA 序列。我们在 130 个 LCL 样本中鉴定出 866 个变异位点，在 130 个血液样本中鉴定出 666 个位点。超过 94%的鉴定出的同质性在 LCL 和血液样本中都存在，而超过 70%的异质性位点仅存在于 LCL 或血液样本中。LCL 和全血样本中每个样本的同质性变异数量相似（p=0.45），而 LCL 每个样本的异质性变异数量多于全血（p<2.2e-16）。此外，LCL 样本倾向于积累低水平的异质性（3-25%的异质性水平），而与其配对的血液样本相比（p=0.001）。这些结果表明，在解释和比较发现时，当应用不同的组织/细胞类型或不同的测序技术来获取 mtDNA 序列时，应该谨慎对待。
