The Human Genome Project was a 13-year-long, publicly funded project initiated in 1990 with the objective of determining the DNA sequence of the entire euchromatic human genome within 15 years. In its early days, the Human Genome Project was met with skepticism by many people, including scientists and nonscientists alike. One prominent question was whether the huge cost of the project would outweigh the potential benefits. Today, however, the overwhelming success of the Human Genome Project is readily apparent. Not only did the completion of this project usher in a new era in medicine, but it also led to significant advances in the types of technology used to sequence DNA.

Initial Principles and Goals of the Human Genome Project

From its inception, the Human Genome Project revolved around two key principles (International Human Genome Sequencing Consortium, 2001). First, it welcomed collaborators from any nation in an effort to move beyond borders, to establish an all-inclusive effort aimed at understanding our shared molecular heritage, and to benefit from diverse approaches. The group of publicly funded researchers that eventually assembled was known as International Human Genome Sequencing Consortium (IHGSC). Second, this project required that all human genome sequence information be freely and publicly available within 24 hours of its assembly. This founding principle ensured unrestricted access for scientists in academia and in industry, and it provided the means for rapid and novel discoveries by researchers of all types. At any given time, approximately 200 labs in the United States were funded by either the National Institutes of Health or the U.S. Department of Energy to support these efforts. In addition, more than 18 different countries from across the globe had contributed to the Human Genome Project by the time of its completion.

Just as the Human Genome Project revolved around two key principles, it also started with two early goals: (1) building genetic and physical maps of the human and mouse genomes, and (2) sequencing the smaller yeast and worm genomes as a test run for sequencing the larger, more complex human genome (IHGSC, 2001). When the yeast and worm efforts proved successful, the sequencing of the human genome proceeded with full force.

Phases of the Human Genome Project

Based on the insights gained from the yeast and worm studies, the Human Genome Project employed a two-phase approach to tackle the human genome sequence (IHGSC, 2001). The first phase, called the shotgun phase, divided human chromosomes into DNA segments of an appropriate size, which were then further subdivided into smaller, overlapping DNA fragments that were sequenced. The Human Genome Project relied upon the physical map of the human genome established earlier, which served as a platform for generating and analyzing the massive amounts of DNA sequence data that emerged from the shotgun phase. Next, the second phase of the project, called the finishing phase, involved filling in gaps and resolving DNA sequences in ambiguous areas not obtained during the shotgun phase. Figure 1 shows the exponential increase in DNA sequence information deposited in the High-Throughput Genomic Sequences (HTGS) division of GenBank by the end of the shotgun phase. Indeed, the shotgun phase yielded 90% of the human genome sequence in draft form.

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