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In February, scientists from the public Human Genome Project and the private company Celera Genomics published the long-awaited details of the working-draft DNA sequence achieved less than a year before. Although the draft is filled with mysteries, the first panoramic view of the human genetic landscape has revealed a wealth of information and some early surprises. Papers describing research observations in the journals Nature (Feb. 15, 2001) and Science (Feb. 16, 2001) are freely accessible via the Web.
Although clearly not a Holy Grail or Rosetta Stone for deciphering all of biology two early metaphors commonly used to describe the coveted prize the sequence is a magnificent and unprecedented resource that will serve as a basis for research and discovery throughout this century and beyond. It will have diverse practical applications and a profound impact upon how we view ourselves and our place in the tapestry of life around us.
One insight already gleaned from the sequence is that, even on the molecular level, we are more than the sum of our 35,000 or so genes. Surprisingly, this newly estimated number of genes is only one-third as great as previously thought and is only twice as many as those of a tiny transparent worm, although the numbers may be revised as more computational and experimental analyses are performed. At once humbled and intrigued by this finding, scientists suggest that the genetic key to human complexity lies not in the number of genes but in how gene parts are used to build different products in a process called alternative splicing. Other sources of added complexity are the thousands of post-translational chemical modifications made to proteins and the repertoire of regulatory mechanisms controlling these processes.
The draft encompasses 90% of the human genome's euchromatic portion, which contains the most genes. In constructing the working draft, the 16 genome sequencing centers produced over 22.1 billion bases of raw sequence data, comprising overlapping fragments totaling 3.9 billion bases and providing sevenfold coverage (sequenced seven times) of the human genome. Over 30% is high-quality, finished sequence, with eight- to tenfold coverage, 99.99% accuracy, and few gaps. All data are freely available via the Web.
The entire working draft will be finished to high quality by 2003. Coincidentally, that year also will be the 50th anniversary of Watson and Crick's publication of DNA structure that launched the era of molecular genetics (www.nature.com/genomics/human/watson-crick). Much will remain to be deciphered even then. Some highlights from Nature, Science, and The Wellcome Trust follow.
Deriving meaningful knowledge from the DNA sequence will define research through the coming decades to inform our understanding of biological systems. This enormous task will require the expertise and creativity of tens of thousands of scientists from varied disciplines in both the public and private sectors worldwide.
The draft sequence already is having an impact on finding genes associated with disease. Over 30 genes have been pinpointed and associated with breast cancer, muscle disease, deafness, and blindness. Additionally, finding the DNA sequences underlying such common diseases as cardiovascular disease, diabetes, arthritis, and cancers is being aided by the human variation maps (SNPs) generated in the HGP in cooperation with the private sector. These genes and SNPs provide focused targets for the development of effective new therapies.
One of the greatest impacts of having the sequence may well be in enabling an entirely new approach to biological research. In the past, researchers studied one or a few genes at a time. With whole-genome sequences and new high-throughput technologies, they can approach questions systematically and on a grand scale. They can study all the genes in a genome, for example, or all the transcripts in a particular tissue or organ or tumor, or how tens of thousands of genes and proteins work together in interconnected networks to orchestrate the chemistry of life.
Post-sequencing projects are well under way worldwide. (See Genomes to Life). These explorations will result in a more comprehensive, new, and profound understanding of complex living systems, with applications to human health, energy, global climate change, and environmental cleanup, among others.
The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v11n3-4).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.