Post-zygotic Point Mutations Are an Underrecognized Source of De Novo Genomic Variation

摘要: De novo mutations are recognized both as an important source of genetic variation and a prominent cause sporadic disease in humans. Mutations identified de generally assumed to have occurred during gametogenesis and, consequently, be present germline events individual. Because Sanger sequencing does not provide the sensitivity reliably distinguish somatic from mutations, proportion that occur somatically rather than remains largely unknown. To determine contribution post-zygotic we analyzed set 107 50 parent-offspring trios. Using four different techniques, found 7 (6.5%) these presumed were fact mosaic blood offspring therefore likely post-zygotically. Furthermore, genome-wide analysis "de novo" variants proband led identification 4/4,081 also detectable one parents, implying parental mosaicism origin variants. Thus, our results show fraction either post-zygotically or inherited consequence low-level parents.