show Abstracthide AbstractThis project generated paired-end sequence data covering the genome of a human male individual to a sequence depth of more than 38x using the Illumina Genome Analyzer. This individual is a member of the population samples described in the PhaseI and PhaseII HapMap Projects and is from the Yoruba in Ibadan, Nigeria (abbreviation: YRI). The DNA identifier for this individual is NA18507, and the DNA sample was obtained from The Coriell Institute for Medical Research. The sequence data have been deposited in the NCBI short read archive under the accession number SRA000271. <P> DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.