For many decades humans have pursued work to characterise the human genome. Today, publicly available references to genome sequences are available and have been instrumental in effecting recent advances in medicine, genetics and technology.
But interpretation of the human genome is in its early stages and large initiatives are now embarking on more complex pursuits to characterise the human genome that include understanding individual genome variation.
What is the human genome sequence?
The human genome sequence is contained in our DNA and is made up of long chains of “base pairs” that form our 23 chromosomes. Along our chromosomes are the base pair sequences that form our 30,000 genes.
All humans share a great degree of similarity in their genome sequences – the same genes are ordered in the same manner across the same chromosomes, yet each of us is unique (except for identical twins) in terms of the exact base pair sequence that makes up our genes and thus our DNA/chromosomes.
It is this similarity that, in a genetic sense, defines us as “human” and the specific variation that defines us as individuals.
Launching the Human Genome Project
As early as the 1980s, momentum was gathering behind activities that supported, and would eventually define, the Human Genome Project.
Conversations had turned into workshops that likened characterisation of the human genome to characterisation of the human anatomy that had centuries earlier revolutionised the practice of medicine.
In 1990, with continued support from the United States Department of Energy, the United States National Institutes of Health (NIH) and widespread international collaboration and cooperation, the $3 billion dollar Human Genome Project was launched.
The project aimed to determine the sequence of the human genome within 15 years. By 2000 (well ahead of schedule) a working draft of the human genome was announced. This was followed by regular updates and refinements and today we all have access to a human “reference genome sequence”.
This sequence does not represent the exact sequence of the base pairs in every human, it is the combined genome sequence of a few individuals and represents the broad architecture of all human genomes that scaffolds current and future work aiming to characterise individual sequence variation.
The detail and stories behind the Human Genome Project are themselves extraordinarily human. This project benefited from our human drive for discovery and advancement and our human response to competition.
It forced us as individuals and communities to consider our personal, ethical and social attitudes towards the availability of human genome information, intellectual property protection (especially gene patenting) and public versus private/commercial enterprise in a broad sense.
Advancing the project's success
In the years after the initiation of the Human Genome Project there were constant and significant advances in key areas that facilitated the enormous DNA sequencing effort.
These advances were achieved in all areas key to the efficient processing of DNA into electronic DNA sequence information. They included:
- improvements in the chemistries and instruments used to decipher the base pair sequences of prepared pieces of DNA
- significant improvements in the capacity of computing facilities to manage the volume and nature of data generated from the instruments
- perhaps most importantly, improvements in the analytical tools
The then state-of-the-art DNA sequencing chemistry used in the Human Genome Project was Sanger sequencing – capable of sequencing single stretches of several hundred base pairs at a time.
Advances in analytical methods of putting these pieces back together into the 3.3 billion base pair human genome was fundamental to the progress of the project.
The Human Genome Project was also advanced by competition. In 1998 a privately funded project with similar aims was launched in the United States by Celera Genomics.
Using a modification of the DNA sequencing technique and a smaller budget it was partly responsible for the accelerated progress of the Human Genome Project.
This competition brought forward other aspects of the project for ethical and legal scrutiny and discussion.
The issue of patenting genes formed a background to the Human Genome Project and many other similarly focused projects for some time. In the early 1990s it had been a serious issue of contention between James Watson and Bernadine Healy (then Director of NIH).
Competition between Celera Genomics and The Human Genome Project now brought the discussion into a different dimension.
The publicly-funded Human Genome Project released new data freely and in 2000 released the first working draft of the genome on the web.
In contrast, Celera filed preliminary patent applications on more than 6,000 genes and also benefited from the data provided by the publicly-funded project.
In March 2000, the US president Bill Clinton announced that the genome could not be patented and should be made freely available.
Within 24 hours of the release of the first draft of the human genome, the scientific community downloaded half a trillion bytes of information from the University of California, Santa Cruz’s genome server – a strong indication of the relevance of this information to the biological, biotechnological and medical research communities.
Interpretation of the genome sequence is in its early stages but has already improved our ability to offer genetic testing and clinical management of many diseases.
We are now embarking on more complex pursuits to characterise the human genome so as to understand individual genome variation. This work is supported by projects related to, and of the same magnitude as, the Human Genome Project, including projects characterising the genomes of other species, among them mice and yeast, the International HapMap Project, The Personal Genome Project and the 1000 Genomes Project.
These projects are greatly enhanced by the next generation of sequencing methodologies, which will expedite the characterisation of the human genome at an individual level in coming years.