Characterizing the Major Structural Variant Alleles of the Human Genome

Peter A. Audano, Arvis Sulovari, Tina A. Graves-Lindsay, Stuart Cantsilieris, Melanie Sorensen, Anne Marie E. Welch, Max L. Dougherty, Bradley J. Nelson, Ankeeta Shah, Susan K. Dutcher, Wesley C. Warren, Vincent Magrini, Sean D. McGrath, Yang I. Li, Richard K. Wilson, Evan E. Eichler

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

In order to provide a comprehensive resource for human structural variants (SVs), we generated long-read sequence data and analyzed SVs for fifteen human genomes. We sequence resolved 99,604 insertions, deletions, and inversions including 2,238 (1.6 Mbp) that are shared among all discovery genomes with an additional 13,053 (6.9 Mbp) present in the majority, indicating minor alleles or errors in the reference. Genotyping in 440 additional genomes confirms the most common SVs in unique euchromatin are now sequence resolved. We report a ninefold SV bias toward the last 5 Mbp of human chromosomes with nearly 55% of all VNTRs (variable number of tandem repeats) mapping to this portion of the genome. We identify SVs affecting coding and noncoding regulatory loci improving annotation and interpretation of functional variation. These data provide the framework to construct a canonical human reference and a resource for developing advanced representations capable of capturing allelic diversity.

Original languageEnglish
Pages (from-to)663-675.e19
JournalCell
Volume176
Issue number3
DOIs
StatePublished - Jan 24 2019

Keywords

  • gap closure
  • human reference genome
  • major allele
  • real-time (SMRT) sequencing
  • single-molecule
  • structural variation
  • whole-genome sequence and assembly

Fingerprint Dive into the research topics of 'Characterizing the Major Structural Variant Alleles of the Human Genome'. Together they form a unique fingerprint.

  • Cite this

    Audano, P. A., Sulovari, A., Graves-Lindsay, T. A., Cantsilieris, S., Sorensen, M., Welch, A. M. E., Dougherty, M. L., Nelson, B. J., Shah, A., Dutcher, S. K., Warren, W. C., Magrini, V., McGrath, S. D., Li, Y. I., Wilson, R. K., & Eichler, E. E. (2019). Characterizing the Major Structural Variant Alleles of the Human Genome. Cell, 176(3), 663-675.e19. https://doi.org/10.1016/j.cell.2018.12.019