title: Assessment of megabase-scale somatic copy number variation using single-cell sequencing.
abstract: 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.
authors.affiliation: Koch Institute for Integrative Cancer Research, Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts 02115, USA;
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Knouse
authors.affiliation: The Barbara K. Ostrom (1978) Bioinformatics and Computing Facility in the Swanson Biotechnology Center, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Koch Institute for Integrative Cancer Research, Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
authors.forename: Angelika
authors.initials: A
authors.lastname: Amon
mesh_terms: D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D018628:Gene Dosage; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008390:Markov Chains; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D059010:Single-Cell Analysis / Q000379:methods