Discovery and quality analysis of a comprehensive set of structural variants and short tandem repeats

Nat Commun. 2020 Jun 10;11(1):2928. doi: 10.1038/s41467-020-16481-5.


Structural variants (SVs) and short tandem repeats (STRs) are important sources of genetic diversity but are not routinely analyzed in genetic studies because they are difficult to accurately identify and genotype. Because SVs and STRs range in size and type, it is necessary to apply multiple algorithms that incorporate different types of evidence from sequencing data and employ complex filtering strategies to discover a comprehensive set of high-quality and reproducible variants. Here we assemble a set of 719 deep whole genome sequencing (WGS) samples (mean 42×) from 477 distinct individuals which we use to discover and genotype a wide spectrum of SV and STR variants using five algorithms. We use 177 unique pairs of genetic replicates to identify factors that affect variant call reproducibility and develop a systematic filtering strategy to create of one of the most complete and well characterized maps of SVs and STRs to date.

Publication types

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

MeSH terms

  • Algorithms
  • Computational Biology
  • Genotype
  • Haplotypes / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Microsatellite Repeats / genetics*
  • Whole Genome Sequencing / methods*