Zong, ChenghangChapman, AlecXie, Xiaoliang2013-03-122012Zong, Chenghang, Alec R. Chapman, and X. Sunney Xie. 2012. Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338(6114): 1622-1626.1095-9203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10386977Kindred 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 a new amplification method: Multiple Annealing and Looping Based Amplification Cycles (MALBAC) that offer 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 call individual single nucleotide variations (SNVs) with no false positives observed. 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.en-UStumor cell lineadenocarcinomageneticscolorectal neoplasmsDNA copy number variationsDNA neoplasmhuman genomehigh-throughput nucleotide sequencinghumansmutation ratenucleic acid amplificationpoint mutationsingle nucleotide polymorphismDNA sequence analysissingle-cell analysisJournal Article2013-03-1210.1126/science.1229164