Assessment of megabase-scale somatic copy number variation using single-cell sequencing

Genome Res. 2016 Mar;26(3):376-84. doi: 10.1101/gr.198937.115. Epub 2016 Jan 15.


Megabase-scale copy number variants (CNVs) can have profound phenotypic consequences. Germline CNVs of this magnitude are associated with disease and experience negative selection. However, it is unknown whether organismal function requires that every cell maintain a balanced genome. It is possible that large somatic CNVs are tolerated or even positively selected. Single-cell sequencing is a useful tool for assessing somatic genomic heterogeneity, but its performance in CNV detection has not been rigorously tested. Here, we develop an approach that allows for reliable detection of megabase-scale CNVs in single somatic cells. We discover large CNVs in 8%-9% of cells across tissues and identify two recurrent CNVs. We conclude that large CNVs can be tolerated in subpopulations of cells, and particular CNVs are relatively prevalent within and across individuals.

Publication types

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

MeSH terms

  • Computational Biology / methods
  • DNA Copy Number Variations*
  • Gene Dosage*
  • Genome, Human
  • Genomics / methods*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Markov Chains
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Single-Cell Analysis* / methods