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Genome-wide detection of single-nucleotide and copy-number variations of a single human cell.

ABSTRACT: 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.

SUBMITTER: Zong C

PROVIDER: S-EPMC3600412 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Genome-wide detection of single-nucleotide and copy-number variations of a single human cell.

Zong Chenghang C Lu Sijia S Chapman Alec R AR Xie X Sunney XS

Science (New York, N.Y.) 20121201 6114

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 m ...[more]

PMID: 23258894

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