Human Genome Project
U.S. Department of Energy

HGP Research Area: Sequencing

DNA Sequencing

One of the primary research areas of the HGP was DNA sequencing.

The HGP’s emphasis was on obtaining a complete and highly accurate reference sequence (1 error in 10,000 bases), largely continuous across each human chromosome. Scientists believe that knowing this sequence is critically important for understanding human biology and for applications to other fields.

A “working draft” of the human genome DNA sequence was completed ahead of schedule in June 2000, published February 2001. The working draft comprises shotgun sequence data from mapped clones, with gaps and ambiguities unresolved. Draft sequence provides a foundation for obtaining the high-quality finished sequence and also is a valuable tool for researchers hunting disease genes. See Feb. 2001 and April 2003 Science and Nature papers analyzing the sequence.

Initial Human DNA Sequence Goals

  • Achieve coverage of at least 90% of the genome in a working draft based on mapped clones by the end of 2001.
  • Finish one-third of the human DNA sequence by the end of 2001.
  • Finish the complete human genome sequence by the end of 2003.
  • Make the sequence totally and freely accessible.

Sequence Variation

A goal also focused on identifying individual variations in the human genome. Although more than 99% of human DNA sequences are the same across the population, variations in DNA sequence can have a major impact on how humans respond to disease; environmental insults such as bacteria, viruses, toxins, and chemicals; and drugs and other therapies.

Methods have been developed to detect different types of variation, particularly the most common type called single-nucleotide polymorphisms (SNPs), which occur about once every 100 to 300 bases. SNP maps are helping scientists identify the multiple genes associated with such complex diseases as cancer, diabetes, vascular disease, and some forms of mental illness. These associations are difficult to establish with conventional gene-hunting methods because a single altered gene may make only a small contribution to disease risk.

Human Genome Sequence Variation Goals

  • Develop technologies for rapid, large-scale identification and scoring of single-nucleotide polymorphisms and other DNA sequence variants.
  • Identify common variants in the coding regions of the majority of identified genes during this 5-year period.
  • Create a SNP map of at least 100,000 markers.
  • Develop the intellectual foundations for studies of sequence variation.
  • Create public resources of DNA samples and cell lines.

Text adapted from F. Collins, Ari Patrinos, et al., “New Goals for the U.S. Human Genome Project: 1998–2003,” Science 282: 682-689 (1998). For a more detailed explanation of sequencing, see the U.S. DOE Primer on Molecular Genetics. See HGP Goals for more details on the project’s goals and their revisions over time.

AreaHGP GoalStandard AchievedDate Achieved
Capacity and Cost of Finished SequenceSequence 500 Mb/year at < $0.25 per finished baseSequence >1,400 Mb/year at <$0.09 per finished baseNovember 2002
Human Sequence Variation100,000 mapped human SNPs3.7 million mapped human SNPsFebruary 2003
DNA Sequence95% of gene-containing part of human sequence finished to 99.99% accuracy99% of gene-containing part of human sequence finished to 99.99% accuracyApril 2003


BAC End Sequencing

Sequence data from both ends of mapped BAC (bacterial artificial chromosomes) clones provide researchers with a series of markers spaced approximately every 3000 to 4000 bases across the genome. Researchers use these markers as “sequence tag connectors” (STCs) to identify the specific clones needing to be sequenced to extend sequenced regions further along the chromosomes and for other uses in large-scale sequencing efforts.