The project to sequence the complete human genome was launched at the end of the 1980s, based on new technology for automated DNA sequencing facilitated by fluorescent detection. The project was initially controversial due to the staggering cost needed to complete it. However, several methodological advances were made in the 1990s, including the concepts of expressed sequence tags (ESTs) and whole-genome assembly based on shotgun sequencing, both first described by Craig Venter’s laboratory. In addition, several technological advances were made, such as more efficient instruments for fluorescent sequencing and the introduction of automated methods for sample preparation. The solid-phase methods for sequencing (see Milestone 2) and the next-generation sequencing methods (see Milestone 3) were also described during this time, but these were not introduced to the research community until several years after the completion of the human genome sequence. In fall 2000, President Clinton held a press conference in the White House to announce that sequencing of the human genome was complete, achieved by both private and public initiatives. The descriptions of the sequencing and analysis efforts were later published in two landmark papers in 2001. In the initial publications, the number of protein-coding genes in the human genome was estimated to be around 40,000, which turned out to be a gross overestimation, and the number has since been revised down to less than 20,000. This effort has allowed the HPA to generate antibodies to proteins corresponding to nearly all of the genes predicted from the genome sequence, including those not studied previously. Thus, the HPA portal has provided the first available information about many thousands of proteins in the human genome.

Key publications

• Venter JC et al., The sequence of the human genome. Science. (2001)
  PubMed: 11181995 DOI: 10.1126/science.1058040

• Lander ES et al., Initial sequencing and analysis of the human genome. Nature. (2001)
  PubMed: 11237011 DOI: 10.1038/35057062

Other selected publications

• Adams MD et al., Complementary DNA sequencing: expressed sequence tags and human genome project. Science. (1991)
  PubMed: 2047873 DOI: 10.1126/science.2047873

• Fleischmann RD et al., Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. (1995)
  PubMed: 7542800 DOI: 10.1126/science.7542800

• Schuler GD et al., A gene map of the human genome. Science. (1996)
  PubMed: 8849440 

• Collins FS et al., New goals for the U.S. Human Genome Project: 1998-2003. Science. (1998)
  PubMed: 9784121 DOI: 10.1126/science.282.5389.682

• Collins FS et al., The Human Genome Project: lessons from large-scale biology. Science. (2003)
  PubMed: 12690187 DOI: 10.1126/science.1084564