Elucidation of de novo small insertion/deletion biology with parent-of-origin phasing.

ABSTRACT: The mechanisms underlying de novo insertion/deletion (indel) genesis, such as polymerase slippage, have been hypothesized but not well characterized in the human genome. We implemented two methodological improvements, which were leveraged to dissect indel mutagenesis. We assigned de novo variants to parent-of-origin (i.e., phasing) with low-coverage long-read whole-genome sequencing, achieving better phasing compared to short-read sequencing (medians of 84% and 23%, respectively). We then wrote an application programming interface to classify indels into three subtypes according to sequence context. Across three cohorts with different phasing methods (N_trios  = 540, all cohorts), we observed that one de novo indel subtype, change in copy count (CCC), was significantly correlated

SUBMITTER: Seiden AH 

PROVIDER: S-EPMC7069802 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature