This paper describes a novel approach to whole human genome sequencing using reversible terminator chemistry. The method involves attaching single molecules of DNA to a flat surface, amplifying them in situ, and using fluorescent reversible terminators for synthetic sequencing. The authors demonstrate the technique by re-sequencing the human genome on flow-sorted X chromosomes and then sequencing the genome of a male Yoruba from Ibadan, Nigeria. They achieve high accuracy and coverage, building an accurate consensus sequence from >30× average depth of paired 35-base reads. The study identifies four million single-nucleotide polymorphisms (SNPs) and four hundred thousand structural variants, many of which were previously unknown. The approach is effective for accurate, rapid, and economical whole-genome re-sequencing and has broad biomedical applications. The authors also discuss the impact of sequence depth on coverage and accuracy, and highlight the potential of massively parallel sequencing technology for clinical and research applications.This paper describes a novel approach to whole human genome sequencing using reversible terminator chemistry. The method involves attaching single molecules of DNA to a flat surface, amplifying them in situ, and using fluorescent reversible terminators for synthetic sequencing. The authors demonstrate the technique by re-sequencing the human genome on flow-sorted X chromosomes and then sequencing the genome of a male Yoruba from Ibadan, Nigeria. They achieve high accuracy and coverage, building an accurate consensus sequence from >30× average depth of paired 35-base reads. The study identifies four million single-nucleotide polymorphisms (SNPs) and four hundred thousand structural variants, many of which were previously unknown. The approach is effective for accurate, rapid, and economical whole-genome re-sequencing and has broad biomedical applications. The authors also discuss the impact of sequence depth on coverage and accuracy, and highlight the potential of massively parallel sequencing technology for clinical and research applications.