This paper introduces a novel whole genome amplification method called Multiple Annealing and Looping Based Amplification Cycles (MALBAC), which significantly reduces bias and improves genome coverage in single cell sequencing. MALBAC is designed to address the limitations of traditional whole genome amplification (WGA) methods, such as PCR-based WGA and Multiple Displacement Amplification (MDA), which often suffer from amplification bias and low genome coverage. The authors demonstrate that MALBAC can achieve 93% genome coverage at ≥2x depth for a single human cell, with a mean sequencing depth of 25x. They used MALBAC to detect digitized copy number variations (CNVs) in a single cancer cell and single nucleotide variations (SNVs) in three kindred cells, achieving high accuracy without false positives. The method also allowed for the direct measurement of the genome-wide mutation rate of a cancer cell line, revealing an unusually high frequency of purine-pyrimidine exchanges among newly acquired SNVs. The study highlights the potential of MALBAC for precise characterization of CNVs and SNVs in single cells, providing insights into the individuality, heterogeneity, and dynamics of genomes.This paper introduces a novel whole genome amplification method called Multiple Annealing and Looping Based Amplification Cycles (MALBAC), which significantly reduces bias and improves genome coverage in single cell sequencing. MALBAC is designed to address the limitations of traditional whole genome amplification (WGA) methods, such as PCR-based WGA and Multiple Displacement Amplification (MDA), which often suffer from amplification bias and low genome coverage. The authors demonstrate that MALBAC can achieve 93% genome coverage at ≥2x depth for a single human cell, with a mean sequencing depth of 25x. They used MALBAC to detect digitized copy number variations (CNVs) in a single cancer cell and single nucleotide variations (SNVs) in three kindred cells, achieving high accuracy without false positives. The method also allowed for the direct measurement of the genome-wide mutation rate of a cancer cell line, revealing an unusually high frequency of purine-pyrimidine exchanges among newly acquired SNVs. The study highlights the potential of MALBAC for precise characterization of CNVs and SNVs in single cells, providing insights into the individuality, heterogeneity, and dynamics of genomes.