Somatic mosaicism is a normal occurrence during development in the tissues and organs. As part of establishing a “healthy population “(HP) background or base-line, we investigated whether such mosaicism can be routinely detected in the circulating DNA secured from a rigorously designed healthy human liquid biopsy clinical trial (saliva, blood). We deployed next generation (NG) whole exome sequencing (WES) at median exome coverage rates of 97.2 % (-to-30x) and 70.0 % (-to-100x). We found that somatic mosaicism is not detectable by such standard bulk WES sequencing assays in saliva and blood DNA in 24 normal healthy Caucasians of both sexes from 18 to 60 years of age. We conclude that for circulating DNA using standard WES no novel somatic mutational variants can be detected in protein-coding regions of normal healthy subjects. This implies that the extent within normal tissues of somatic mosaicism must be at a lower level, below the detection threshold, for these circulating DNA WES read depths.

体细胞镶嵌症是组织和器官发育过程中的正常现象。作为建立“健康人群”（HP）背景或基线的一部分，我们调查了是否可以从经过严格设计的健康人类液体活检临床试验（唾液，血液）中获得的循环DNA中常规检测到这种镶嵌现象。我们部署了下一代（NG）全外显子组测序（WES），中位外显子组覆盖率分别为97.2％（至30倍）和70.0％（至100倍）。我们发现，在18至60岁的24名男女正常健康的白种人中，唾液和血液DNA中的此类标准批量WES测序分析无法检测到体细胞镶嵌症。我们得出结论，对于使用标准WES循环DNA而言，在正常健康受试者的蛋白质编码区域中无法检测到新的体细胞突变变异体。