Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

STAR Protoc. 2021 Mar 10;2(1):100383. doi: 10.1016/j.xpro.2021.100383. eCollection 2021 Mar 19.


Here, we present a protocol to analyze de novo genetic variants derived from the whole-exome sequencing (WES) of proband-parent trios. We provide stepwise instructions for using existing pipelines to call de novo mutations (DNMs) and determine whether the observed number of such mutations is enriched relative to the expected number. This protocol may be extended to any human disease trio-based cohort. Cohort size is a limiting determinant to the discovery of high-confidence pathogenic DNMs. For complete details on the use and execution of this protocol, please refer to Dong et al. (2020).

Keywords: Bioinformatics; Genetics; Genomics; High-throughput screening; Sequence analysis; Sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Exome / genetics
  • Exome Sequencing / methods*
  • Family
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / genetics*
  • Humans
  • Mutation / genetics
  • Parents
  • Sequence Analysis, DNA / methods*
  • Workflow