Journal
SCIENCE
Volume 338, Issue 6114, Pages 1622-1626Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1229164
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Funding
- U.S. National Institutes of Health National Human Genome Research Institute [HG005097-1, HG005613-01]
- Bill & Melinda Gates Foundation [OPP42867]
- NIH [NIH/NIGMS T32 GM008313]
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Kindred cells can have different genomes because of dynamic changes in DNA. Single-cell sequencing is needed to characterize these genomic differences but has been hindered by whole-genome amplification bias, resulting in low genome coverage. Here, we report on a new amplification method-multiple annealing and looping-based amplification cycles (MALBAC)-that offers high uniformity across the genome. Sequencing MALBAC-amplified DNA achieves 93% genome coverage >= 1x for a single human cell at 25x mean sequencing depth. We detected digitized copy-number variations (CNVs) of a single cancer cell. By sequencing three kindred cells, we were able to identify individual single-nucleotide variations (SNVs), with no false positives detected. We directly measured the genome-wide mutation rate of a cancer cell line and found that purine-pyrimidine exchanges occurred unusually frequently among the newly acquired SNVs.
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